Activation of anterior HOX genes in hindbrain development during early embryogenesis (Homo sapiens)

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2, 5, 10, 13-15, 18...9, 35, 38, 41, 438, 44, 46, 677, 35, 38, 41, 431, 12, 24, 30, 33...471, 514, 12, 24, 306, 16, 37, 629, 38251239, 38, 39, 50, 5319, 32, 33, 38, 41...39, 401, 38, 5139, 40, 44, 46139, 40, 47728, 39, 409, 382220, 26, 639, 386, 16, 19, 35, 37...9, 41, 43, 56, 642936, 449, 38nucleoplasmcytosolPOLR2E EZH2 Me3K5-HIST1H3A HIST1H2BB HOXD4 gene H2AFV POLR2K RARA Me3K-28-HIST2H3A Me3K5-H3F3A HIST1H2BM EZH2 HIST1H2BH H2AFZ HIST2H2AC EZH2 RBBP5 ASH2L HIST1H2BM POLR2I HIST1H2BC HIST1H2BJ HIST3H2BB POLR2B WDR5 PCGF2HIST1H4 H2AFV POLR2C HOXA2 bivalentchromatinRBBP4 HIST1H2AD H2AFJ HOXC4 gene PBX1 HIST1H2BN Me3K-28-HIST1H3A NCOR1Me3K5-HIST1H3A HIST2H2BE Me3K-28-H3F3A HIST1H2BL HIST1H4 HIST1H2BJ NCOA6 HIST1H2AD HIST1H2BJ HIST2H2BE Me3K-28-H3F3A HIST1H2AC POLR2K HOXD1 gene PAXIP1 H2AFV MEIS1HIST1H2AD HIST1H2BC EED H2AFB1 POLR2L HIST2H2AA3 HIST1H2AD H2AFJ POLR2K RNA Polymerase IIholoenzyme complex(generic)Me3K5-HIST2H3A POLR2L HOXB1 geneHOXB3 geneHIST2H2AC HIST1H2BB KDM6A RBBP5 H2BFS H2AFV PAXIP1 HIST1H2BD POLR2I HIST2H2AC POLR2J HIST1H2BJ HOXB2HOXB2 mRNAHIST2H2AA3 H2BFS HIST1H2AJ HIST1H2BO H2AFZ HIST1H2BK POLR2F HIST1H2BA Me3K-28-H3F3A POLR2A POLR2D HIST1H2AC POLR2I POLR2K H2AFX HOXA4 gene HIST2H2AA3 HIST1H2AJ H2AFV SUZ12 HIST1H2BM ASH2L HIST1H2BA HIST1H2AC H2AFZ PAGR1 WDR5 HIST1H2BD KMT2D PAXIP1 HIST3H2BB POLR2L NCOA3 POLR2K RBBP7 HIST1H2BM HIST1H2BJ POLR2F HIST1H2BD HIST1H2BH KMT2D H2AFV PAGR1 HIST1H2AC POLR2G HOXA1HIST1H2BD H2AFB1 Me3K-28-HIST1H3A PAXIP1 HIST1H2BN HIST1H2BB atRA PKNOX1 H2AFB1 atRA Me3K5-HIST1H3A HOXD4POLR2G KDM6A HIST1H2BM HIST1H2BL HIST3H2BB HIST1H2BD RBBP5 PAXIP1 Me3K5-H3F3A HOXB4 mRNAMe3K5-HIST2H3A H2AFB1 HIST1H2BC Me3K-28-HIST1H3A H2AFX HIST2H2AA3 POLR2B HOXA2 gene HIST1H2BA H2AFX H2AFJ KMT2C RBBP7 HIST1H2AD RARA POLR2A Me3K5-HIST1H3A H2AFX HIST1H2BC RBBP4 HIST2H2AC Me3K5-HIST1H3A AJUBAHIST1H2BL HIST1H2BO POLR2G HIST1H2AB HIST2H2AC RBBP4 H2AFZ POLR2J POLR2B Me3K-28-HIST2H3A Me3K5-H3F3A POLR2C JUNRARG HIST1H2BA POLR2C HIST1H2BM H2AFZ Me3K5-H3F3A HIST1H4 Me3K5-H3F3A HOXB3 gene POLR2E H2AFV POLR2B H2AFJ HIST2H2AC POLR2H HIST1H2AD HIST1H2AB HIST1H2BH HIST1H2BO WDR5 H2AFJ EP300 HOXB1 POLR2J HIST1H4 HIST1H2AC POLR2C HIST2H2AC PAGR1 H2AFX HIST2H2BE HIST1H2BN HIST1H2AB RXRA HIST1H2BB HIST1H2BM ASH2L HIST1H2AB H2AFB1 HIST2H2AC HIST1H2BD POLR2I HIST1H2BJ Me3K-28-H3F3A HOXC4 activechromatinHIST1H2BD Me3K5-HIST1H3A HIST1H2BO Me3K5-H3F3A POLR2L HIST1H2BN ASH2L HIST1H2AC HIST2H2AC HIST1H4 HIST1H2BO RBBP7 WDR5 HIST1H2BJ HIST1H2AD HIST1H2BK HIST1H2AJ HIST1H4 POLR2H HIST1H2BM HIST1H2BJ Me3K5-HIST1H3A HIST2H2AA3 HIST3H2BB Me3K-28-HIST1H3A Me3K5-HIST2H3A RBBP4 Me3K5-H3F3A H2AFZ POLR2C POLR2J HIST1H2BM HIST2H2AA3 HIST3H2BB HIST1H2BH MEIS1 HIST1H2BK WDR5 HIST1H2BH SUZ12 atRA:RARA,B:RXRA atactive HOXD4chromatinHIST1H2BD H2BFS HIST1H2BN RARA Me3K5-H3F3A HIST1H2BC HIST1H2BL HIST1H2BD RARA,G:RXRA at HOXB1bivalent chromatinWDR5 PBX1:PKNOX1CREBBP Me3K5-HIST1H3A HIST1H2AC HIST3H2BB POLR2G HIST1H2AJ POLR2G POLR2D HIST1H2AC CTCF POLR2B POLR2L POLR2A POLR2B NCOA6 POLR2F H2AFV NCOR1 PKNOX1 KMT2C Me3K5-HIST1H3A Me3K5-HIST1H3A POLR2J HIST2H2AA3 RBBP4 POLR2C HIST1H2BO HIST1H2BC RBBP5 PAX6HIST1H2BB POLR2A HIST3H2BB HIST2H2AC HOXA2 activechromatinPOLR2A HIST1H2BO HIST1H2BA H2AFV HIST1H2BC HIST1H4 HIST2H2AC Me3K5-H3F3A H2AFV HIST1H2AB HIST1H2BH HIST1H2BO H2BFS POLR2A Me3K5-HIST1H3A POLR2H POLR2E HIST1H2AB HOXB1 gene Me3K5-HIST2H3A HIST1H2BL Me3K5-HIST2H3A HIST1H4 POLR2B POLR2L HIST1H4 HIST1H2AC H2BFS HIST1H2BD POLR2I HIST1H2BO HIST1H2BL Me3K-28-H3F3A Me3K5-HIST2H3A H2BFS H2BFS HIST1H2AD HIST2H2AC HIST3H2BB H2AFJ Me3K5-H3F3A HIST1H2BC HIST3H2BB HIST1H4 H2AFZ HIST1H2BD POLR2D POLR2I POLR2H HIST1H2BD HIST1H2AJ POLR2K POLR2D HIST1H2BM ASH2L H2AFX NCOA6 Me3K5-HIST2H3A H2AFJ HIST1H2BA H2AFZ HIST1H2BD H2AFX HOXA1 gene HIST2H2AC RARG PAGR1 H2AFZ POLR2F HIST1H2BD HIST1H2AC ASH2L HIST1H2AB Me3K-28-HIST1H3A H2AFJ HOXA3 bivalentchromatinHIST1H2BA H2AFJ HIST1H2BO HIST1H2BK KMT2C HIST1H2BJ HIST1H2BD RBBP5 HIST1H2AD HIST1H2BJ HIST1H2BK HIST1H2BL RBBP5 POLR2E HIST1H2BD RARA,B:RXRA at HOXB4bivalent chromatinH2AFJ HIST1H2BB HOXD3 gene HIST1H2BL HIST1H2AJ H2AFB1 H2AFV POLR2L HIST2H2AC RBBP5 HIST1H2BK HIST1H2BL Me3K5-HIST2H3A KDM6A CTCF HOXB4 geneHIST3H2BB HIST1H2BO HOXD1 geneHIST1H2BB HOXB4 gene HIST1H2BJ HIST2H2BE HIST1H2AJ ZNF335 SUZ12 HIST2H2AC RARA,B:RXRA at HOXD4bivalent chromatinASH2L HIST1H2BA RBBP5 H2AFB1 HIST1H2BC H2BFS HIST2H2AA3 HIST1H2BL HIST1H2BN POLR2A H2AFB1 HIST1H2BO HIST1H2AB POLR2H POLR2A HIST2H2AA3 H2AFV HIST1H2AD EGR2HIST1H2BC HIST1H2BD HIST1H2BN PAXIP1 HIST3H2BB POLR2E POLR2J H2AFB1 KMT2D EZH2 HIST1H2BH Me3K5-HIST2H3A EZH2 H2AFZ HIST3H2BB HIST1H2BO RARA POLR2G Me3K5-HIST2H3A KDM6A KMT2C PAXIP1 H2AFB1 NCOA6 HIST1H2BN HIST1H2BC HIST1H2BH HIST1H2BC RBBP7 H2AFB1 HIST1H2BK Me3K-28-HIST1H3A Me3K5-H3F3A HOXA1 geneHIST1H2AD POLR2H Me3K5-HIST2H3A EGR2 Me3K5-HIST2H3A HIST1H2BC HIST1H2BK H2AFV Me3K-28-HIST2H3A HIST1H2BO NCOR1 HIST1H2BB HOXB2 gene NCOA6 HIST2H2AA3 HIST2H2AA3 HIST2H2AC RBBP4 POLR2K H2AFZ EED EZH2 POLR2C HIST1H2BB Me3K-28-HIST2H3A PAGR1 HOXA3 gene SUZ12 HIST1H2BD SUZ12 HIST1H2AD HIST1H4 MEIS1 H2AFB1 H2AFX HIST1H2BN RXRA HIST1H2AJ HIST1H2BN POLR2F HIST2H2BE POLR2K RARB HIST3H2BB H2AFX RXRA PRC2 (EZH2) CoreHIST1H2AJ EED NCOA3NCOA6 EZH2 H2AFV RBBP7 HIST1H2BB KMT2D HIST1H2AJ H2AFX HIST1H2BN POLR2C HIST1H2AC POLR2E HIST1H4 SUZ12 WDR5 H2AFX Me3K5-HIST2H3A WDR5 HOXD1HIST2H2BE POLR2J H2AFZ HIST1H2BK YY1 H2AFV HIST1H2BL HIST1H2BC HIST1H2AB POLR2H HIST1H2BO Me3K5-HIST1H3A HIST1H2BN POLR2F H2AFJ HIST1H2BA PKNOX1 H2AFJ PAGR1 PAGR1 POLR2B HOXD4 mRNARARB POLR2H HOXB3PAGR1 H2AFZ RBBP5 KDM6A HIST1H2BL SUZ12 H2AFJ HIST1H4 HIST1H2BD RXRA HIST1H2AC HIST2H2AA3 H2AFJ H2AFV HIST2H2AA3 HIST1H2AD HIST1H2BK H2AFV HOXA4H2BFS HIST1H2BN HOXC4 mRNAHIST1H2AC PBX1:PKNOX1EED CTCF RARB HIST1H2AJ H2AFZ HIST1H2BA POLR2A POLR2H HIST1H2BK HIST1H2BO POLR2J HIST1H2BA POLR2J HIST1H2BA HOXB1 gene H2AFV KMT2C H2BFS HIST2H2BE POLR2I H2AFZ HIST1H4 NCOA6 Me3K5-H3F3A EZH2 HIST1H2BL HIST2H2AA3 atRA:RARA,G:RXRA atactive HOXB1chromatinHIST1H2BL HIST1H2AJ ASH2L H2AFX PAGR1 HIST2H2AA3 PBX1 POLR2I Me3K5-HIST1H3A H2AFX KDM6A POLR2E POLR2C POLR2B HIST3H2BB KMT2C PBX1 Me3K5-HIST1H3A HIST1H2BB HIST2H2AC HIST3H2BB EZH2 ASH2L RARG HIST2H2AA3 H2BFS HIST1H2BC PBX1 POLR2A HIST1H2BL POLR2K POLR2L EGR2POLR2J HIST1H2BB Me3K5-HIST2H3A KDM6A RBBP5 PAXIP1 KMT2C HIST1H2AB H2AFB1 HIST1H2BA HIST1H2BA KDM6A MAFBHIST1H2BN HIST1H4 H2BFS HIST1H2BN RARB HIST1H2BA HIST2H2BE HIST1H2BO HIST3H2BB HIST2H2AA3 POLR2D H2BFS PAGR1 Me3K5-HIST2H3A YY1 HIST2H2BE HIST1H2AB HIST1H2BM HIST1H2BK HIST1H2BD Me3K-28-HIST2H3A KMT2D PAXIP1 Me3K5-HIST2H3A H2AFX H2AFB1 POLR2I HIST1H2BK HIST1H2AD H2AFB1 NCOA6 HOXB3 gene POLR2H HIST1H2BM POLR2I HIST1H2BJ HIST1H2BA H2AFZ HIST1H4 HIST1H2BJ PAGR1 HIST1H2BK HOXB3 gene HIST1H2BM HIST1H2BO KMT2C HIST1H2BH HIST1H2BC Me3K5-HIST2H3A HIST1H2BB HIST1H2BK HIST1H2AB NCOR1 HIST1H2BN HIST3H2BB KMT2D HIST1H2BC MAFB Me3K5-HIST2H3A Me3K5-HIST2H3A RXRA HOXA3 gene POLR2E HIST1H4 HIST1H2BL HIST2H2AC RBBP4 Me3K5-HIST1H3A HIST1H2AJ HOXD3 gene Me3K5-HIST2H3A HIST1H2BB HOXB2 bivalentchromatinHIST1H2BO PAXIP1 HIST1H2BC H2BFS H2BFS KDM6A HIST1H2AC HIST2H2BE H2AFZ HIST1H2AC POLR2C HIST1H2AD HIST1H2BA HIST1H2BM HIST1H2BM HIST1H2BC HIST1H2BH HIST1H2BB HIST2H2BE HIST1H4 KDM6A H2AFZ RXRA HIST1H2BK HOXB1 mRNAPOLR2B SUZ12 POLR2E HIST1H2BL HOXA1 mRNAH2AFX HIST1H2AB RBBP5 HIST2H2AC HOXD3 mRNAHIST1H2AC POLR2L H2AFZ Me3K-28-H3F3A EP300 HIST1H2AD HIST1H2BA HOXA4 gene POLR2E HIST1H2BJ POLR2I POLR2G RARG POLR2K HOXC4EGR2 H2AFJ Me3K5-H3F3A RARA,B:RXRA at HOXA4bivalent chromatinPOLR2D HIST1H2BH POLR2E PAXIP1 KMT2C HIST2H2AA3 POLR2F H2AFJ POLR2F HIST3H2BB H2AFZ POLR2A HOXD3 geneHOXA3POLR2E HIST1H2BJ HIST2H2AC SUZ12 POLR2F HIST1H4 HIST3H2BB Me3K5-H3F3A HIST1H2BD HIST1H2AC KMT2D HIST1H2BA H2AFX H2AFX HIST1H4 HIST1H2BN HIST1H2BD HIST2H2AC POLR2E Me3K5-HIST1H3A Me3K5-H3F3A H2AFV PKNOX1 H2AFV HIST1H2AJ POLR2A HDAC3HIST1H2BL HIST1H2BO HIST1H2BJ H2AFZ KMT2C PAGR1 HIST2H2BE POLR2F HIST1H2AB CNOT6 HIST1H2BC HOXA3 gene Me3K5-HIST1H3A H2AFJ HIST1H2AB RBBP7 HIST1H2BM HIST2H2BE HIST1H4 EGR2 at active HOXA2chromatinH2AFV HIST1H2BH HIST1H2AB H2BFS HIST1H2BA HIST1H2AC HIST1H2AJ POLR2I POLR2B HOXD1 gene PBX1 RARA,G:RXRA at HOXA1bivalent chromatinHIST1H2BM RBBP4 MAFB:JUN and EGR2 atactive HOXB3chromatinHIST1H2AJ RBBP7 Me3K5-H3F3A HIST1H2AB ASH2L RBBP5 POLR2D POLR2I Me3K-28-HIST2H3A HIST2H2AA3 HOXB1:PBX1:PKNOX1 atactive HOXA2chromatinKMT2C HIST1H2BD HIST1H2BB KDM6A HIST1H2BJ HIST1H2BB H2AFX HIST1H2AB HOXA2 mRNAHIST1H2BL atRA POLR2G H2BFS KMT2D H2AFX HIST2H2AC H2AFX atRA H2AFX POLR2K HIST1H2BO HOXB3 mRNAHIST2H2AA3 HIST1H2BJ Me3K5-HIST1H3A Me3K-28-HIST1H3A H2AFV HIST1H2BJ HIST1H2BL POLR2L HIST1H2BJ KMT2D H2AFZ H2AFZ HIST1H2BC HIST1H2BL H2AFZ HIST3H2BB POLR2G HIST1H2BB POLR2K POLR2H HIST1H2BM HIST1H2BN HIST1H2BO PAXIP1 NCOA3 HIST2H2BE Me3K5-HIST1H3A PKNOX1 H2AFV HIST1H2AJ H2AFB1 Me3K5-H3F3A POLR2L POLR2I PKNOX1 H2AFZ Me3K5-HIST2H3A HIST1H2BJ HIST1H2BN RARA POLR2K HIST2H2AC MAFB,HOXB1:PBX1:PKNOX1at active HOXA3chromatinHIST1H2AC POLR2L WDR5 POLR2G POLR2H POLR2D RBBP7 NCOA6 HIST1H2AB KMT2C HIST1H2AD Me3K-28-HIST1H3A HIST2H2BE PIAS2RBBP4 Me3K-28-H3F3A POLR2K HIST1H2BO POLR2J Me3K5-HIST1H3A POLR2F Me3K5-H3F3A HIST1H2BC H2AFV H2BFS ASH2L HIST1H2AD POLR2L HIST1H2BH Me3K5-HIST2H3A HIST1H2AD HIST1H2BB HIST1H2BB HIST2H2AA3 HIST2H2AC Me3K-28-HIST1H3A POLR2H HIST1H2BO HIST1H2BK HIST1H2AJ HOXA3 mRNANCOA6 HIST1H2BD HIST1H2BO HIST1H2BN HIST1H2AJ EED H2AFZ H2AFJ H2AFX HIST1H4 EED H2AFB1 Me3K-28-HIST2H3A H2AFB1 ASH2L HIST1H2BA PAX6 HIST1H2BK MLL2,3 complexH2AFB1 HIST1H2BO HIST1H2BB HIST2H2AA3 HOXB3 bivalentchromatinHOXA2 gene POLR2B HOXA4 genePOLR2J H2AFZ CREBBPRBBP4 NCOA3 HIST1H2BJ HIST1H2BB H2AFV KMT2C HIST3H2BB PBX1:PKNOX1,MEIS1SUZ12 HIST1H2BM Me3K5-HIST2H3A H2AFX KMT2D EP300 POLR2B H2AFB1 CTCF KMT2C HIST1H2AC POLR2C HOXC4 geneHOXA1 gene H2BFS HIST2H2BE HIST3H2BB KDM6A HIST1H2BH HIST1H2AJ HOXB2 gene HIST1H2BJ HIST1H2AJ H2AFX HIST1H2BB RBBP7 PBX1 HIST1H2AC PAGR1 H2AFX HIST1H2AJ HIST1H2AB HIST1H2AC RBBP5 HIST1H2BM HIST1H4 atRA:RARA,B:RXRA atactive HOXB4chromatinHIST1H2BH HIST2H2BE RBBP4 POLR2I HIST2H2BE HIST1H2BJ HIST1H2BB Me3K5-HIST2H3A KMT2C Me3K-28-HIST1H3A HDAC3 POLR2J HIST1H2BN POLR2B SUZ12 RXRA H2AFB1 atRA:RARA,G:RXRA atactive HOXA1chromatinHOXB3 activechromatinHIST1H2AB HIST1H2AC POLR2D Me3K5-HIST2H3A KMT2D HOXA2HIST1H2AD HIST1H2AJ HIST2H2AA3 HIST3H2BB H2AFB1 POLR2F RBBP4 HIST1H2BK HIST3H2BB HIST1H2BL HIST2H2AA3 Me3K5-H3F3A HIST1H2BD HIST1H2AB Me3K5-H3F3A HIST1H4 HIST2H2BE HIST1H2BJ Me3K-28-H3F3A WDR5 HIST1H2BL HIST1H2BM HIST1H2BO HIST1H2BD ASH2L POLR2D EGR2HIST1H2BC HIST1H2BH Me3K5-H3F3A H2BFS Me3K5-H3F3A POLR2E H2AFX POLR2G POLR2B H2BFS NCOA3 H2AFJ HIST1H2BK HIST1H2BD HIST1H2BM Me3K-28-HIST2H3A RBBP7 H2AFV Me3K5-HIST2H3A HIST1H2AD POLR2A NCOA6 POLR2E POLR2A H2AFJ HIST1H2BA HOXA3 activechromatinWDR5 HIST1H2BJ HIST1H2BK HOXB4 gene Me3K5-H3F3A HIST2H2BE HIST1H2BA HIST3H2BB NCOR1 HIST2H2BE HIST1H2BH H2AFB1 HIST1H2BK HIST1H2BK HIST1H2BA RARB HIST1H2AC Me3K5-HIST2H3A Me3K5-H3F3A H2AFJ PBX1 HIST2H2AC POLR2A RARA KDM6A PAXIP1 EED H2AFJ Me3K-28-HIST2H3A NCOA6 HIST1H2AD KDM6A PKNOX1 PAGR1 HIST1H2AB H2AFZ RXRA H2BFS PAGR1 RQCD1HIST1H2AC H2AFB1 MEIS1 HOXB1POLR2J HIST1H2AC HIST1H2AD HIST1H2AD HIST1H2BA HOXB1 NCOA3 H2AFB1 Me3K-28-H3F3A HIST3H2BB HOXB1 PAXIP1 HIST1H2BD HIST1H2BK H2AFB1 HIST1H2AC HIST1H2AJ KMT2D Me3K5-H3F3A RBBP5 HIST1H2AD HIST1H2BL HIST1H2BB POLR2F POLR2D HOXA2 geneHIST1H2BC Me3K-28-HIST2H3A HIST1H2BK HIST1H2BH POLR2C RBBP5 EZH2 HIST1H2BL H2AFX Me3K5-HIST1H3A HIST1H2BH HIST1H2AB Me3K5-HIST2H3A HIST1H4 Me3K5-HIST1H3A Me3K5-HIST1H3A HOXA2 gene HIST1H4 Me3K5-HIST1H3A HOXD1 activechromatinHIST1H2AJ H2AFV H2AFV HIST1H2BM H2AFB1 HIST1H2BB HIST1H2BA H2AFB1 NCOA6 HOXB1:PBX1:PKNOX1and MEIS1 at activeHOXB1 chromatinHIST1H2AC H2AFJ HIST3H2BB Me3K5-HIST1H3A RBBP4 HIST1H2BM HIST1H2BN KDM6A POLR2E Me3K5-HIST1H3A POLR2K Me3K5-H3F3A HIST1H2BO EED EGR2 at active HOXB2chromatinMe3K5-H3F3A RBBP7 HOXA2 gene HIST2H2AA3 HIST1H2AD H2AFJ HIST2H2AC HIST2H2AC PBX1 HIST2H2AA3 H2AFJ WDR5 H2BFS HIST2H2AC HIST1H2BN NCOR1 H2AFV H2BFS HIST1H2AC HIST1H2BM H2BFS WDR5 HIST1H2BB HIST2H2BE HOXD4 gene HIST1H2BN POLR2F HIST3H2BB Me3K5-HIST1H3A HIST1H2BK HIST2H2AA3 H2AFX Me3K5-H3F3A Me3K5-H3F3A RXRA HIST1H2BH HOXB2 genePAXIP1 HIST1H2AJ HIST1H2BL HIST1H2BJ HIST1H2AB HIST1H2BH POLR2K POLR2L HIST1H2BA HIST1H2BJ HIST1H2BO HIST2H2BE HOXB1 HIST2H2BE Me3K-28-H3F3A HOXD3HIST1H2BB HIST1H2BN H2AFJ H2BFS EGR2HIST1H2BO POLR2D HOXD3 activechromatinH2AFZ KMT2D RARB POLR2G HIST1H2BA atRA Me3K-28-HIST1H3A HIST1H2BA HOXB4HIST1H2AB HIST2H2AC HIST1H2AB POLR2F HOXD1 mRNAH2AFX HIST1H2BD H2BFS HIST1H2BD WDR5 KMT2D EED HOXB2 activechromatinPOLR2D Me3K5-HIST1H3A HIST1H2BO HOXC4 gene POLR2D H2BFS HIST1H2BN POLR2G HIST1H2BJ HOXA4 mRNAPAGR1 HIST1H4 HIST1H2AD H2AFZ H2AFB1 HIST1H2BM RBBP7 RBBP5 POLR2H HIST2H2BE Me3K-28-HIST2H3A HOXB2 gene H2AFJ H2BFS Me3K-28-HIST2H3A NCOA6 PCGF2 PAXIP1 POLR2J HIST1H2AJ HIST2H2BE RARA HIST1H4 HIST1H2BB H2AFJ H2AFV HIST2H2BE Me3K-28-HIST1H3A EED HIST2H2BE HIST1H2AJ EZH2 HIST1H2BA HIST1H2BC HIST1H2BD EP300 HIST1H2BN ASH2L HIST1H2BK POLR2L SUZ12 HIST1H2BK HIST1H2BA HIST2H2BE HIST1H2BL POLR2F HIST3H2BB RXRA EP300HIST1H2AJ POLR2B HIST1H2BL HIST2H2BE HIST1H2BH Me3K5-HIST1H3A HIST1H2AB atRAEED Me3K-28-H3F3A Me3K5-HIST2H3A NCOA6 POLR2C HIST1H2BM H2AFB1 Me3K5-H3F3A Me3K5-HIST1H3A HOXC4 bivalentchromatinSUZ12 POLR2I HOXD3 bivalentchromatinPOLR2C HIST1H2BL HIST1H2BH HIST1H2BH POLR2C HIST1H2AB PKNOX1 HIST1H2BM HIST1H2BM HIST1H2BC HOXD4 geneHIST1H2BC HIST2H2AC HIST1H2BH EED HIST1H2AD HIST2H2AC CNOT6:ZNF335HIST2H2AA3 HIST1H2AJ HIST1H2AD HIST2H2AA3 HIST2H2AA3 HIST1H2AC HOXB2 gene HIST1H2BH ASH2L HIST1H2BB HIST1H2BC H2BFS POLR2G KMT2D HIST1H2BL POLR2C HIST1H2BC EED POLR2G HIST1H2AJ HIST1H2BK HIST1H2BC HIST1H2AD H2AFB1 WDR5 HOXA3 geneHIST1H2BH ASH2L POLR2D HIST1H2BH HIST2H2BE Me3K5-HIST1H3A HIST2H2AA3 POLR2G KMT2D EP300 H2AFJ HIST1H2BJ HIST1H2AC HOXD1 bivalentchromatinJUN HIST1H4 H2AFJ HIST1H2BN H2AFX POLR2L HIST1H2BH POLR2J HIST1H2BN POLR2H HOXB1 gene RARA HIST1H2BL AJUBA HIST1H2AD HIST1H2BK H2BFS H2AFX HIST1H2AB MAFB HIST3H2BB HOXB1:PBX1:MEIS1,PKNOX1 at active HOXB2 chromatinH2AFV NCOA6 Me3K5-H3F3A EZH2 HIST1H2BB HIST1H4 HIST1H2BN Me3K-28-H3F3A PBX1:PKNOX1POLR2D HIST1H2BM RARA EZH2 KDM6A HIST1H2BH HIST3H2BB KMT2C HIST1H2BJ RBBP7 EGR2 H2AFZ HIST1H2BK Me3K5-HIST2H3A HIST1H2BM POLR2H RARA H2AFJ Me3K5-HIST2H3A HIST1H2BH HIST1H2BC POLR2A WDR5 HIST1H2BN HIST1H4 HIST1H2AB atRA:RARA,B:RXRA atactive HOXA4chromatin357, 35, 38, 419, 383, 11, 17, 27, 429, 3819, 389, 38259, 35, 38, 419, 41, 649, 381, 38, 519, 381, 12, 24, 30, 33...2599, 35, 38, 419, 389, 389, 41, 649, 382519, 389, 38, 53351, 38, 51459, 381, 12, 24, 30, 33...9, 38, 539, 38


Description

In mammals, anterior Hox genes may be defined as paralog groups 1 to 4 (Natale et al. 2011), which are involved in development of the hindbrain through sequential expression in the rhombomeres, transient segments of the neural tube that form during development of the hindbrain (reviewed in Alexander et al. 2009, Soshnikova and Duboule 2009, Tumpel et al. 2009, Mallo et al. 2010, Andrey and Duboule 2014). Hox gene activation during mammalian development has been most thoroughly studied in mouse embryos and the results have been extended to human development by in vitro experiments with human embryonal carcinoma cells and human embryonic stem cells.
Expression of a typical anterior Hox gene has an anterior boundary located at the junction between two rhombomeres and continues caudally to regulate segmentation and segmental fate in ectoderm, mesoderm, and endoderm. Anterior boundaries of expression of successive Hox paralog groups are generally separated from each other by 2 rhombomeres. For example, HOXB2 is expressed in rhombomere 3 (r3) and caudally while HOXB3 is expressed in r5 and caudally. Exceptions exist, however, as HOXA1, HOXA2, and HOXB1 do not follow the rule and HOXD1 and HOXC4 are not expressed in rhombomeres. Hox genes within a Hox cluster are expressed colinearly: the gene at the 3' end of the cluster is expressed earliest, and hence most anteriorly, then genes 5' are activated sequentially in the same order as they occur in the cluster.
Activation of expression occurs epigenetically by loss of polycomb repressive complexes and change of bivalent chromatin to active chromatin through, in part, the actions of trithorax family proteins (reviewed in Soshnikova and Duboule 2009). Hox gene expression initiates in the posterior primitive streak that will contribute to extraembryonic mesoderm. Expression then extends anteriorly into the cells that will become the embryo, where expression is first observed in presumptive lateral plate mesoderm and is transmitted to both paraxial mesoderm and neurectoderm formed by gastrulation along the primitive streak (reviewed in Deschamps et al. 1999, Casaca et al. 2014).
Prior to establishment of the rhombomeres, expression of HOXA1 and HOXB1 is initiated near the future site of r3 and caudally by a gradient of retinoic acid (RA). (Mechanisms of retinoic acid signaling are reviewed in Cunningham and Duester 2015.) The RA is generated by the ALDH1A2 (RALDH2) enzyme located in somites flanking the caudal hindbrain and degraded by CYP26 enzymes expressed initially in anterior neural ectoderm of the early gastrula and then throughout most of the hindbrain (reviewed in White and Schilling 2008). HOXA1 with PBX1,2 and MEIS2 directly activate transcription of ALDH1A2 to maintain retinoic acid synthesis in the somitic mesoderm (Vitobello et al. 2011). Differentiation of embryonal carcinoma cells and embryonic stem cells in response to retinoic acid is used to model the process of differentiation in vitro (reviewed in Soprano et al. 2007, Gudas et al. 2013).
HOXA1 appears to set the anterior limit of HOXB1 expression (Barrow et al. 2000). HOXB1 initiates expression of EGR2 (KROX20) in presumptive r3. EGR2 then activates HOXA2 expression in r3 and r5 while HOXB1, together with PBX1 and MEIS:PKNOX1 (MEIS:PREP), activates expression of HOXA2 in r4 and caudal rhombomeres. AP-2 transcription factors maintain expression of HOXA2 in neural crest cells (Maconochie et al. 1999). HOXB1 also activates expression of HOXB2 in r3 and caudal rhombomeres. EGR2 negatively regulates HOXB1 so that by the time rhombomeres appear, HOXB1 is restricted to r4 and HOXA1 is no longer detectable (Barrow et al. 2000). EGR2 and MAFB (Kreisler) then activate HOXA3 and HOXB3 in r5 and caudal rhombomeres. Retinoic acid activates HOXA4, HOXB4, and HOXD4 in r7, the final rhombomere. HOX proteins, in turn, activate expression of genes in combination with other factors, notably members of the TALE family of transcription factors (PBX, PREP, and MEIS, reviewed in Schulte and Frank 2014, Rezsohazy et al. 2015). HOX proteins also participate in non-transcriptional interactions (reviewed in Rezsohazy 2014). In zebrafish, Xenopus, and chicken factors such as Meis3, Fgf3, Fgf8, and vHNF regulate anterior hox genes (reviewed in Schulte and Frank 2014), however less is known about the roles of homologous factors in mammals.
Mutations in HOXA1 in humans have been observed to cause developmental abnormalities located mostly in the head and neck region (Tischfield et al. 2005, Bosley et al. 2008). A missense mutation in HOXA2 causes microtia, hearing impairment, and partially cleft palate (Alasti et al. 2008). A missense mutation in HOXB1 causes a similar phenotype to the Hoxb1 null mutation in mice: bilateral facial palsy, hearing loss, and strabismus (improper alignment of the eyes) (Webb et al. 2012). View original pathway at:Reactome.

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Pathway is converted from Reactome ID: 5617472
Reactome-version 
Reactome version: 65
Reactome Author 
Reactome Author: May, Bruce

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Bibliography

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  1. Maconochie M, Krishnamurthy R, Nonchev S, Meier P, Manzanares M, Mitchell PJ, Krumlauf R.; ''Regulation of Hoxa2 in cranial neural crest cells involves members of the AP-2 family.''; PubMed Europe PMC Scholia
  2. Segara D, Biankin AV, Kench JG, Langusch CC, Dawson AC, Skalicky DA, Gotley DC, Coleman MJ, Sutherland RL, Henshall SM.; ''Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia.''; PubMed Europe PMC Scholia
  3. Manohar CF, Salwen HR, Furtado MR, Cohn SL.; ''Up-regulation of HOXC6, HOXD1, and HOXD8 homeobox gene expression in human neuroblastoma cells following chemical induction of differentiation.''; PubMed Europe PMC Scholia
  4. Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y.; ''Role of histone H3 lysine 27 methylation in Polycomb-group silencing.''; PubMed Europe PMC Scholia
  5. Zhai J, Lin H, Canete-Soler R, Schlaepfer WW.; ''HoxB2 binds mutant SOD1 and is altered in transgenic model of ALS.''; PubMed Europe PMC Scholia
  6. Ciferri C, Lander GC, Maiolica A, Herzog F, Aebersold R, Nogales E.; ''Molecular architecture of human polycomb repressive complex 2.''; PubMed Europe PMC Scholia
  7. Simeone A, Acampora D, Arcioni L, Andrews PW, Boncinelli E, Mavilio F.; ''Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells.''; PubMed Europe PMC Scholia
  8. Weiss FU, Marques IJ, Woltering JM, Vlecken DH, Aghdassi A, Partecke LI, Heidecke CD, Lerch MM, Bagowski CP.; ''Retinoic acid receptor antagonists inhibit miR-10a expression and block metastatic behavior of pancreatic cancer.''; PubMed Europe PMC Scholia
  9. Deschamps J, van den Akker E, Forlani S, De Graaff W, Oosterveen T, Roelen B, Roelfsema J.; ''Initiation, establishment and maintenance of Hox gene expression patterns in the mouse.''; PubMed Europe PMC Scholia
  10. Kuzmichev A, Jenuwein T, Tempst P, Reinberg D.; ''Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3.''; PubMed Europe PMC Scholia
  11. Fernandez CC, Gudas LJ.; ''The truncated Hoxa1 protein interacts with Hoxa1 and Pbx1 in stem cells.''; PubMed Europe PMC Scholia
  12. Webb BD, Shaaban S, Gaspar H, Cunha LF, Schubert CR, Hao K, Robson CD, Chan WM, Andrews C, MacKinnon S, Oystreck DT, Hunter DG, Iacovelli AJ, Ye X, Camminady A, Engle EC, Jabs EW.; ''HOXB1 founder mutation in humans recapitulates the phenotype of Hoxb1-/- mice.''; PubMed Europe PMC Scholia
  13. Alexander T, Nolte C, Krumlauf R.; ''Hox genes and segmentation of the hindbrain and axial skeleton.''; PubMed Europe PMC Scholia
  14. Gudas LJ.; ''Retinoids induce stem cell differentiation via epigenetic changes.''; PubMed Europe PMC Scholia
  15. Mallo M, Wellik DM, Deschamps J.; ''Hox genes and regional patterning of the vertebrate body plan.''; PubMed Europe PMC Scholia
  16. Morrison A, Ariza-McNaughton L, Gould A, Featherstone M, Krumlauf R.; ''HOXD4 and regulation of the group 4 paralog genes.''; PubMed Europe PMC Scholia
  17. Tümpel S, Wiedemann LM, Krumlauf R.; ''Hox genes and segmentation of the vertebrate hindbrain.''; PubMed Europe PMC Scholia
  18. Rezsohazy R, Saurin AJ, Maurel-Zaffran C, Graba Y.; ''Cellular and molecular insights into Hox protein action.''; PubMed Europe PMC Scholia
  19. Doerksen LF, Bhattacharya A, Kannan P, Pratt D, Tainsky MA.; ''Functional interaction between a RARE and an AP-2 binding site in the regulation of the human HOX A4 gene promoter.''; PubMed Europe PMC Scholia
  20. Chen J, Zhu S, Jiang N, Shang Z, Quan C, Niu Y.; ''HoxB3 promotes prostate cancer cell progression by transactivating CDCA3.''; PubMed Europe PMC Scholia
  21. Rezsohazy R.; ''Non-transcriptional interactions of Hox proteins: inventory, facts, and future directions.''; PubMed Europe PMC Scholia
  22. Klein ES, Wang JW, Khalifa B, Gavigan SA, Chandraratna RA.; ''Recruitment of nuclear receptor corepressor and coactivator to the retinoic acid receptor by retinoid ligands. Influence of DNA-heterodimer interactions.''; PubMed Europe PMC Scholia
  23. Chen D, Sun Y, Yuan Y, Han Z, Zhang P, Zhang J, You MJ, Teruya-Feldstein J, Wang M, Gupta S, Hung MC, Liang H, Ma L.; ''miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion.''; PubMed Europe PMC Scholia
  24. Chariot A, Moreau L, Senterre G, Sobel ME, Castronovo V.; ''Retinoic acid induces three newly cloned HOXA1 transcripts in MCF7 breast cancer cells.''; PubMed Europe PMC Scholia
  25. Yekta S, Tabin CJ, Bartel DP.; ''MicroRNAs in the Hox network: an apparent link to posterior prevalence.''; PubMed Europe PMC Scholia
  26. Berthelsen J, Zappavigna V, Ferretti E, Mavilio F, Blasi F.; ''The novel homeoprotein Prep1 modulates Pbx-Hox protein cooperativity.''; PubMed Europe PMC Scholia
  27. Han L, Witmer PD, Casey E, Valle D, Sukumar S.; ''DNA methylation regulates MicroRNA expression.''; PubMed Europe PMC Scholia
  28. Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D.; ''Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein.''; PubMed Europe PMC Scholia
  29. Zhan M, Qu Q, Wang G, Liu YZ, Tan SL, Lou XY, Yu J, Zhou HH.; ''Let-7c inhibits NSCLC cell proliferation by targeting HOXA1.''; PubMed Europe PMC Scholia
  30. Soprano DR, Teets BW, Soprano KJ.; ''Role of retinoic acid in the differentiation of embryonal carcinoma and embryonic stem cells.''; PubMed Europe PMC Scholia
  31. Cunningham TJ, Duester G.; ''Mechanisms of retinoic acid signalling and its roles in organ and limb development.''; PubMed Europe PMC Scholia
  32. Giampaolo A, Acampora D, Zappavigna V, Pannese M, D'Esposito M, Carè A, Faiella A, Stornaiuolo A, Russo G, Simeone A.; ''Differential expression of human HOX-2 genes along the anterior-posterior axis in embryonic central nervous system.''; PubMed Europe PMC Scholia
  33. Tan Y, Zhang B, Wu T, Skogerbø G, Zhu X, Guo X, He S, Chen R.; ''Transcriptional inhibiton of Hoxd4 expression by miRNA-10a in human breast cancer cells.''; PubMed Europe PMC Scholia
  34. Andrey G, Duboule D.; ''SnapShot: Hox gene regulation.''; PubMed Europe PMC Scholia
  35. Xu M, Zhao GN, Lv X, Liu G, Wang LY, Hao DL, Wang J, Liu DP, Liang CC.; ''CTCF controls HOXA cluster silencing and mediates PRC2-repressive higher-order chromatin structure in NT2/D1 cells.''; PubMed Europe PMC Scholia
  36. Palakurthy RK, Wajapeyee N, Santra MK, Gazin C, Lin L, Gobeil S, Green MR.; ''Epigenetic silencing of the RASSF1A tumor suppressor gene through HOXB3-mediated induction of DNMT3B expression.''; PubMed Europe PMC Scholia
  37. Di Rocco G, Mavilio F, Zappavigna V.; ''Functional dissection of a transcriptionally active, target-specific Hox-Pbx complex.''; PubMed Europe PMC Scholia
  38. Chen D, Chen Z, Jin Y, Dragas D, Zhang L, Adjei BS, Wang A, Dai Y, Zhou X.; ''MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells.''; PubMed Europe PMC Scholia
  39. White RJ, Schilling TF.; ''How degrading: Cyp26s in hindbrain development.''; PubMed Europe PMC Scholia
  40. Bosley TM, Alorainy IA, Salih MA, Aldhalaan HM, Abu-Amero KK, Oystreck DT, Tischfield MA, Engle EC, Erickson RP.; ''The clinical spectrum of homozygous HOXA1 mutations.''; PubMed Europe PMC Scholia
  41. Cao R, Zhang Y.; ''SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex.''; PubMed Europe PMC Scholia
  42. Sessa L, Breiling A, Lavorgna G, Silvestri L, Casari G, Orlando V.; ''Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster.''; PubMed Europe PMC Scholia
  43. Sakamoto Y, Watanabe S, Ichimura T, Kawasuji M, Koseki H, Baba H, Nakao M.; ''Overlapping roles of the methylated DNA-binding protein MBD1 and polycomb group proteins in transcriptional repression of HOXA genes and heterochromatin foci formation.''; PubMed Europe PMC Scholia
  44. Yates JA, Menon T, Thompson BA, Bochar DA.; ''Regulation of HOXA2 gene expression by the ATP-dependent chromatin remodeling enzyme CHD8.''; PubMed Europe PMC Scholia
  45. Alasti F, Sadeghi A, Sanati MH, Farhadi M, Stollar E, Somers T, Van Camp G.; ''A mutation in HOXA2 is responsible for autosomal-recessive microtia in an Iranian family.''; PubMed Europe PMC Scholia
  46. Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, Story M, Le QT, Giaccia AJ.; ''Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation.''; PubMed Europe PMC Scholia
  47. Lee MG, Villa R, Trojer P, Norman J, Yan KP, Reinberg D, Di Croce L, Shiekhattar R.; ''Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination.''; PubMed Europe PMC Scholia
  48. Sengupta PK, Lavelle DE, DeSimone J.; ''The 87-kD A gamma-globin enhancer-binding protein is a product of the HOXB2(HOX2H) locus.''; PubMed Europe PMC Scholia
  49. Shpargel KB, Starmer J, Yee D, Pohlers M, Magnuson T.; ''KDM6 demethylase independent loss of histone H3 lysine 27 trimethylation during early embryonic development.''; PubMed Europe PMC Scholia
  50. Vitobello A, Ferretti E, Lampe X, Vilain N, Ducret S, Ori M, Spetz JF, Selleri L, Rijli FM.; ''Hox and Pbx factors control retinoic acid synthesis during hindbrain segmentation.''; PubMed Europe PMC Scholia
  51. Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, Chen S, Iwase S, Alpatov R, Issaeva I, Canaani E, Roberts TM, Chang HY, Shi Y.; ''A histone H3 lysine 27 demethylase regulates animal posterior development.''; PubMed Europe PMC Scholia
  52. Garzon R, Pichiorri F, Palumbo T, Iuliano R, Cimmino A, Aqeilan R, Volinia S, Bhatt D, Alder H, Marcucci G, Calin GA, Liu CG, Bloomfield CD, Andreeff M, Croce CM.; ''MicroRNA fingerprints during human megakaryocytopoiesis.''; PubMed Europe PMC Scholia
  53. Lonfat N, Duboule D.; ''Structure, function and evolution of topologically associating domains (TADs) at HOX loci.''; PubMed Europe PMC Scholia
  54. Moroni MC, Viganó MA, Mavilio F.; ''Regulation of the human HOXD4 gene by retinoids.''; PubMed Europe PMC Scholia
  55. Rousseau M, Crutchley JL, Miura H, Suderman M, Blanchette M, Dostie J.; ''Hox in motion: tracking HoxA cluster conformation during differentiation.''; PubMed Europe PMC Scholia
  56. Tischfield MA, Bosley TM, Salih MA, Alorainy IA, Sener EC, Nester MJ, Oystreck DT, Chan WM, Andrews C, Erickson RP, Engle EC.; ''Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development.''; PubMed Europe PMC Scholia
  57. Ogura T, Evans RM.; ''A retinoic acid-triggered cascade of HOXB1 gene activation.''; PubMed Europe PMC Scholia
  58. Agger K, Cloos PA, Christensen J, Pasini D, Rose S, Rappsilber J, Issaeva I, Canaani E, Salcini AE, Helin K.; ''UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development.''; PubMed Europe PMC Scholia
  59. Soshnikova N, Duboule D.; ''Epigenetic regulation of vertebrate Hox genes: a dynamic equilibrium.''; PubMed Europe PMC Scholia
  60. Zappavigna V, Renucci A, Izpisúa-Belmonte JC, Urier G, Peschle C, Duboule D.; ''HOX4 genes encode transcription factors with potential auto- and cross-regulatory capacities.''; PubMed Europe PMC Scholia
  61. Morrison A, Moroni MC, Ariza-McNaughton L, Krumlauf R, Mavilio F.; ''In vitro and transgenic analysis of a human HOXD4 retinoid-responsive enhancer.''; PubMed Europe PMC Scholia
  62. Zha Y, Ding E, Yang L, Mao L, Wang X, McCarthy BA, Huang S, Ding HF.; ''Functional dissection of HOXD cluster genes in regulation of neuroblastoma cell proliferation and differentiation.''; PubMed Europe PMC Scholia
  63. Koller K, Das S, Leuschner I, Korbelius M, Hoefler G, Guertl B.; ''Identification of the transcription factor HOXB4 as a novel target of miR-23a.''; PubMed Europe PMC Scholia
  64. Li Q, Zhu F, Chen P.; ''miR-7 and miR-218 epigenetically control tumor suppressor genes RASSF1A and Claudin-6 by targeting HoxB3 in breast cancer.''; PubMed Europe PMC Scholia
  65. Garapaty S, Mahajan MA, Samuels HH.; ''Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1.''; PubMed Europe PMC Scholia
  66. Bocker MT, Tuorto F, Raddatz G, Musch T, Yang FC, Xu M, Lyko F, Breiling A.; ''Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster.''; PubMed Europe PMC Scholia
  67. Barrow JR, Stadler HS, Capecchi MR.; ''Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
114944view16:46, 25 January 2021ReactomeTeamReactome version 75
113062view10:59, 2 November 2020ReactomeTeamReactome version 74
112296view15:12, 9 October 2020ReactomeTeamReactome version 73
101509view11:37, 1 November 2018ReactomeTeamreactome version 66
101045view21:18, 31 October 2018ReactomeTeamreactome version 65
100576view19:52, 31 October 2018ReactomeTeamreactome version 64
100125view16:37, 31 October 2018ReactomeTeamreactome version 63
99675view15:07, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99269view12:45, 31 October 2018ReactomeTeamreactome version 62
93879view13:42, 16 August 2017ReactomeTeamreactome version 61
93446view11:23, 9 August 2017ReactomeTeamreactome version 61
87076view14:21, 18 July 2016MkutmonOntology Term : 'regulatory pathway' added !
86538view09:20, 11 July 2016ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AJUBA ProteinQ96IF1 (Uniprot-TrEMBL)
AJUBAProteinQ96IF1 (Uniprot-TrEMBL)
ASH2L ProteinQ9UBL3 (Uniprot-TrEMBL)
CNOT6 ProteinQ9ULM6 (Uniprot-TrEMBL)
CNOT6:ZNF335ComplexR-HSA-6810135 (Reactome)
CREBBP ProteinQ92793 (Uniprot-TrEMBL)
CREBBPProteinQ92793 (Uniprot-TrEMBL)
CTCF ProteinP49711 (Uniprot-TrEMBL)
EED ProteinO75530 (Uniprot-TrEMBL)
EGR2 ProteinP11161 (Uniprot-TrEMBL)
EGR2 at active HOXA2 chromatinComplexR-HSA-5617477 (Reactome)
EGR2 at active HOXB2 chromatinComplexR-HSA-5617489 (Reactome)
EGR2ProteinP11161 (Uniprot-TrEMBL)
EP300 ProteinQ09472 (Uniprot-TrEMBL)
EP300ProteinQ09472 (Uniprot-TrEMBL)
EZH2 ProteinQ15910 (Uniprot-TrEMBL)
H2AFB1 ProteinP0C5Y9 (Uniprot-TrEMBL)
H2AFJ ProteinQ9BTM1 (Uniprot-TrEMBL)
H2AFV ProteinQ71UI9 (Uniprot-TrEMBL)
H2AFX ProteinP16104 (Uniprot-TrEMBL)
H2AFZ ProteinP0C0S5 (Uniprot-TrEMBL)
H2BFS ProteinP57053 (Uniprot-TrEMBL)
HDAC3 ProteinO15379 (Uniprot-TrEMBL)
HDAC3ProteinO15379 (Uniprot-TrEMBL)
HIST1H2AB ProteinP04908 (Uniprot-TrEMBL)
HIST1H2AC ProteinQ93077 (Uniprot-TrEMBL)
HIST1H2AD ProteinP20671 (Uniprot-TrEMBL)
HIST1H2AJ ProteinQ99878 (Uniprot-TrEMBL)
HIST1H2BA ProteinQ96A08 (Uniprot-TrEMBL)
HIST1H2BB ProteinP33778 (Uniprot-TrEMBL)
HIST1H2BC ProteinP62807 (Uniprot-TrEMBL)
HIST1H2BD ProteinP58876 (Uniprot-TrEMBL)
HIST1H2BH ProteinQ93079 (Uniprot-TrEMBL)
HIST1H2BJ ProteinP06899 (Uniprot-TrEMBL)
HIST1H2BK ProteinO60814 (Uniprot-TrEMBL)
HIST1H2BL ProteinQ99880 (Uniprot-TrEMBL)
HIST1H2BM ProteinQ99879 (Uniprot-TrEMBL)
HIST1H2BN ProteinQ99877 (Uniprot-TrEMBL)
HIST1H2BO ProteinP23527 (Uniprot-TrEMBL)
HIST1H4 ProteinP62805 (Uniprot-TrEMBL)
HIST2H2AA3 ProteinQ6FI13 (Uniprot-TrEMBL)
HIST2H2AC ProteinQ16777 (Uniprot-TrEMBL)
HIST2H2BE ProteinQ16778 (Uniprot-TrEMBL)
HIST3H2BB ProteinQ8N257 (Uniprot-TrEMBL)
HOXA1 gene ProteinENSG00000105991 (Ensembl)
HOXA1 geneGeneProductENSG00000105991 (Ensembl)
HOXA1 mRNARnaENST00000343060 (Ensembl)
HOXA1ProteinP49639 (Uniprot-TrEMBL)
HOXA2 active chromatinComplexR-HSA-6810133 (Reactome)
HOXA2 bivalent chromatinComplexR-HSA-5617490 (Reactome)
HOXA2 gene ProteinENSG00000105996 (Ensembl)
HOXA2 geneGeneProductENSG00000105996 (Ensembl)
HOXA2 mRNARnaENST00000222718 (Ensembl)
HOXA2ProteinO43364 (Uniprot-TrEMBL)
HOXA3 active chromatinComplexR-HSA-6810160 (Reactome)
HOXA3 bivalent chromatinComplexR-HSA-5617645 (Reactome)
HOXA3 gene ProteinENSG00000105997 (Ensembl)
HOXA3 geneGeneProductENSG00000105997 (Ensembl)
HOXA3 mRNARnaENST00000317201 (Ensembl)
HOXA3ProteinO43365 (Uniprot-TrEMBL)
HOXA4 gene ProteinENSG00000197576 (Ensembl)
HOXA4 geneGeneProductENSG00000197576 (Ensembl)
HOXA4 mRNARnaENST00000360046 (Ensembl)
HOXA4ProteinQ00056 (Uniprot-TrEMBL)
HOXB1 ProteinP14653 (Uniprot-TrEMBL)
HOXB1 gene ProteinENSG00000120094 (Ensembl)
HOXB1 geneGeneProductENSG00000120094 (Ensembl)
HOXB1 mRNARnaENST00000239174 (Ensembl)
HOXB1:PBX1:MEIS1,PKNOX1 at active HOXB2 chromatinComplexR-HSA-5621009 (Reactome)
HOXB1:PBX1:PKNOX1

and MEIS1 at active

HOXB1 chromatin
ComplexR-HSA-5693638 (Reactome)
HOXB1:PBX1:PKNOX1 at

active HOXA2

chromatin
ComplexR-HSA-5621001 (Reactome)
HOXB1ProteinP14653 (Uniprot-TrEMBL)
HOXB2 active chromatinComplexR-HSA-6810166 (Reactome)
HOXB2 bivalent chromatinComplexR-HSA-5617482 (Reactome)
HOXB2 gene ProteinENSG00000173917 (Ensembl)
HOXB2 geneGeneProductENSG00000173917 (Ensembl)
HOXB2 mRNARnaENST00000330070 (Ensembl)
HOXB2ProteinP14652 (Uniprot-TrEMBL)
HOXB3 active chromatinComplexR-HSA-6810168 (Reactome)
HOXB3 bivalent chromatinComplexR-HSA-5617644 (Reactome)
HOXB3 gene ProteinENSG00000120093 (Ensembl)
HOXB3 geneGeneProductENSG00000120093 (Ensembl)
HOXB3 mRNARnaENST00000311626 (Ensembl)
HOXB3ProteinP14651 (Uniprot-TrEMBL)
HOXB4 gene ProteinENSG00000182742 (Ensembl)
HOXB4 geneGeneProductENSG00000182742 (Ensembl)
HOXB4 mRNARnaENST00000332503 (Ensembl)
HOXB4ProteinP17483 (Uniprot-TrEMBL)
HOXC4 active chromatinComplexR-HSA-5617870 (Reactome)
HOXC4 bivalent chromatinComplexR-HSA-5617885 (Reactome)
HOXC4 gene ProteinENSG00000198353 (Ensembl)
HOXC4 geneGeneProductENSG00000198353 (Ensembl)
HOXC4 mRNARnaENST00000303406 (Ensembl)
HOXC4ProteinP09017 (Uniprot-TrEMBL)
HOXD1 active chromatinComplexR-HSA-5617453 (Reactome)
HOXD1 bivalent chromatinComplexR-HSA-5617473 (Reactome)
HOXD1 gene ProteinENSG00000128645 (Ensembl)
HOXD1 geneGeneProductENSG00000128645 (Ensembl)
HOXD1 mRNARnaENST00000331462 (Ensembl)
HOXD1ProteinQ9GZZ0 (Uniprot-TrEMBL)
HOXD3 active chromatinComplexR-HSA-5617663 (Reactome)
HOXD3 bivalent chromatinComplexR-HSA-5617662 (Reactome)
HOXD3 gene ProteinENSG00000128652 (Ensembl)
HOXD3 geneGeneProductENSG00000128652 (Ensembl)
HOXD3 mRNARnaENST00000249440 (Ensembl)
HOXD3ProteinP31249 (Uniprot-TrEMBL)
HOXD4 gene ProteinENSG00000170166 (Ensembl)
HOXD4 geneGeneProductENSG00000170166 (Ensembl)
HOXD4 mRNARnaENST00000306324 (Ensembl)
HOXD4ProteinP09016 (Uniprot-TrEMBL)
JUN ProteinP05412 (Uniprot-TrEMBL)
JUNProteinP05412 (Uniprot-TrEMBL)
KDM6A ProteinO15550 (Uniprot-TrEMBL)
KMT2C ProteinQ8NEZ4 (Uniprot-TrEMBL)
KMT2D ProteinO14686 (Uniprot-TrEMBL)
MAFB ProteinQ9Y5Q3 (Uniprot-TrEMBL)
MAFB,

HOXB1:PBX1:PKNOX1 at active HOXA3

chromatin
ComplexR-HSA-5617651 (Reactome)
MAFB:JUN and EGR2 at

active HOXB3

chromatin
ComplexR-HSA-5617671 (Reactome)
MAFBProteinQ9Y5Q3 (Uniprot-TrEMBL)
MEIS1 ProteinO00470 (Uniprot-TrEMBL)
MEIS1ProteinO00470 (Uniprot-TrEMBL)
MLL2,3 complexComplexR-HSA-5619379 (Reactome)
Me3K-28-H3F3A ProteinP84243 (Uniprot-TrEMBL)
Me3K-28-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
Me3K-28-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
Me3K5-H3F3A ProteinP84243 (Uniprot-TrEMBL)
Me3K5-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
Me3K5-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
NCOA3 ProteinQ9Y6Q9 (Uniprot-TrEMBL)
NCOA3ProteinQ9Y6Q9 (Uniprot-TrEMBL)
NCOA6 ProteinQ14686 (Uniprot-TrEMBL)
NCOR1 ProteinO75376 (Uniprot-TrEMBL)
NCOR1ProteinO75376 (Uniprot-TrEMBL)
PAGR1 ProteinQ9BTK6 (Uniprot-TrEMBL)
PAX6 ProteinP26367 (Uniprot-TrEMBL)
PAX6ProteinP26367 (Uniprot-TrEMBL)
PAXIP1 ProteinQ6ZW49 (Uniprot-TrEMBL)
PBX1 ProteinP40424 (Uniprot-TrEMBL)
PBX1:PKNOX1,MEIS1ComplexR-HSA-5693631 (Reactome)
PBX1:PKNOX1ComplexR-HSA-5693627 (Reactome)
PCGF2 ProteinP35227 (Uniprot-TrEMBL)
PCGF2ProteinP35227 (Uniprot-TrEMBL)
PIAS2ProteinO75928 (Uniprot-TrEMBL)
PKNOX1 ProteinP55347 (Uniprot-TrEMBL)
POLR2A ProteinP24928 (Uniprot-TrEMBL)
POLR2B ProteinP30876 (Uniprot-TrEMBL)
POLR2C ProteinP19387 (Uniprot-TrEMBL)
POLR2D ProteinO15514 (Uniprot-TrEMBL)
POLR2E ProteinP19388 (Uniprot-TrEMBL)
POLR2F ProteinP61218 (Uniprot-TrEMBL)
POLR2G ProteinP62487 (Uniprot-TrEMBL)
POLR2H ProteinP52434 (Uniprot-TrEMBL)
POLR2I ProteinP36954 (Uniprot-TrEMBL)
POLR2J ProteinP52435 (Uniprot-TrEMBL)
POLR2K ProteinP53803 (Uniprot-TrEMBL)
POLR2L ProteinP62875 (Uniprot-TrEMBL)
PRC2 (EZH2) CoreComplexR-HSA-212285 (Reactome) The human Polycomb Repressive Complex 2 (PRC2) is homologous to the Drosophila PRC2. The core PRC2 contains EZH2, a histone methyltransferase specific for lysine 27 and lysine 9 of histone H3. The methyltransferase activity of EZH2 is dependent on its association with PRC2. The complex contains other uncharacterized proteins, its composition may vary in different tissues and developmental stages, and the order of assembly of the complex is presently unknown.
RARA ProteinP10276 (Uniprot-TrEMBL)
RARA,B:RXRA at HOXA4 bivalent chromatinComplexR-HSA-5617876 (Reactome)
RARA,B:RXRA at HOXB4 bivalent chromatinComplexR-HSA-5617880 (Reactome)
RARA,B:RXRA at HOXD4 bivalent chromatinComplexR-HSA-5617895 (Reactome)
RARA,G:RXRA at HOXA1 bivalent chromatinComplexR-HSA-5617465 (Reactome)
RARA,G:RXRA at HOXB1 bivalent chromatinComplexR-HSA-5617474 (Reactome)
RARB ProteinP10826 (Uniprot-TrEMBL)
RARG ProteinP13631 (Uniprot-TrEMBL)
RBBP4 ProteinQ09028 (Uniprot-TrEMBL)
RBBP5 ProteinQ15291 (Uniprot-TrEMBL)
RBBP7 ProteinQ16576 (Uniprot-TrEMBL)
RNA Polymerase II

holoenzyme complex

(generic)
ComplexR-HSA-209680 (Reactome)
RQCD1ProteinQ92600 (Uniprot-TrEMBL)
RXRA ProteinP19793 (Uniprot-TrEMBL)
SUZ12 ProteinQ15022 (Uniprot-TrEMBL)
WDR5 ProteinP61964 (Uniprot-TrEMBL)
YY1 ProteinP25490 (Uniprot-TrEMBL)
ZNF335 ProteinQ9H4Z2 (Uniprot-TrEMBL)
atRA MetaboliteCHEBI:15367 (ChEBI)
atRA:RARA,B:RXRA at

active HOXA4

chromatin
ComplexR-HSA-5617873 (Reactome)
atRA:RARA,B:RXRA at

active HOXB4

chromatin
ComplexR-HSA-5617888 (Reactome)
atRA:RARA,B:RXRA at

active HOXD4

chromatin
ComplexR-HSA-5617861 (Reactome)
atRA:RARA,G:RXRA at

active HOXA1

chromatin
ComplexR-HSA-5617448 (Reactome)
atRA:RARA,G:RXRA at

active HOXB1

chromatin
ComplexR-HSA-5617470 (Reactome)
atRAMetaboliteCHEBI:15367 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
AJUBAArrowR-HSA-5617431 (Reactome)
CNOT6:ZNF335ArrowR-HSA-5617471 (Reactome)
CREBBPR-HSA-5617896 (Reactome)
EGR2 at active HOXA2 chromatinArrowR-HSA-5617483 (Reactome)
EGR2 at active HOXA2 chromatinArrowR-HSA-5617484 (Reactome)
EGR2 at active HOXB2 chromatinArrowR-HSA-5617486 (Reactome)
EGR2 at active HOXB2 chromatinArrowR-HSA-5617492 (Reactome)
EGR2R-HSA-5617484 (Reactome)
EGR2R-HSA-5617492 (Reactome)
EGR2R-HSA-5617661 (Reactome)
EGR2TBarR-HSA-5617454 (Reactome)
EP300R-HSA-5617431 (Reactome)
EP300R-HSA-5617452 (Reactome)
EP300R-HSA-5617859 (Reactome)
EP300R-HSA-5617862 (Reactome)
EP300R-HSA-5617896 (Reactome)
HDAC3ArrowR-HSA-5617431 (Reactome)
HOXA1 geneR-HSA-5617471 (Reactome)
HOXA1 mRNAArrowR-HSA-5617471 (Reactome)
HOXA1 mRNAR-HSA-5617458 (Reactome)
HOXA1ArrowR-HSA-5617452 (Reactome)
HOXA1ArrowR-HSA-5617458 (Reactome)
HOXA2 active chromatinArrowR-HSA-6810139 (Reactome)
HOXA2 active chromatinR-HSA-5617484 (Reactome)
HOXA2 active chromatinR-HSA-5621010 (Reactome)
HOXA2 bivalent chromatinR-HSA-6810139 (Reactome)
HOXA2 geneR-HSA-5617483 (Reactome)
HOXA2 mRNAArrowR-HSA-5617483 (Reactome)
HOXA2 mRNAR-HSA-5617479 (Reactome)
HOXA2ArrowR-HSA-5617479 (Reactome)
HOXA3 active chromatinArrowR-HSA-6810161 (Reactome)
HOXA3 active chromatinR-HSA-5617641 (Reactome)
HOXA3 bivalent chromatinR-HSA-6810161 (Reactome)
HOXA3 geneR-HSA-5617676 (Reactome)
HOXA3 mRNAArrowR-HSA-5617676 (Reactome)
HOXA3 mRNAR-HSA-5617643 (Reactome)
HOXA3ArrowR-HSA-5617643 (Reactome)
HOXA4 geneR-HSA-5617877 (Reactome)
HOXA4 mRNAArrowR-HSA-5617877 (Reactome)
HOXA4 mRNAR-HSA-5617879 (Reactome)
HOXA4ArrowR-HSA-5617879 (Reactome)
HOXB1 geneR-HSA-5617454 (Reactome)
HOXB1 mRNAArrowR-HSA-5617454 (Reactome)
HOXB1 mRNAR-HSA-5617457 (Reactome)
HOXB1:PBX1:MEIS1,PKNOX1 at active HOXB2 chromatinArrowR-HSA-5617486 (Reactome)
HOXB1:PBX1:MEIS1,PKNOX1 at active HOXB2 chromatinArrowR-HSA-5621002 (Reactome)
HOXB1:PBX1:PKNOX1

and MEIS1 at active

HOXB1 chromatin
ArrowR-HSA-5617454 (Reactome)
HOXB1:PBX1:PKNOX1

and MEIS1 at active

HOXB1 chromatin
ArrowR-HSA-5693644 (Reactome)
HOXB1:PBX1:PKNOX1 at

active HOXA2

chromatin
ArrowR-HSA-5617483 (Reactome)
HOXB1:PBX1:PKNOX1 at

active HOXA2

chromatin
ArrowR-HSA-5621010 (Reactome)
HOXB1ArrowR-HSA-5617457 (Reactome)
HOXB1R-HSA-5617641 (Reactome)
HOXB1R-HSA-5621002 (Reactome)
HOXB1R-HSA-5621010 (Reactome)
HOXB1R-HSA-5693644 (Reactome)
HOXB2 active chromatinArrowR-HSA-6810159 (Reactome)
HOXB2 active chromatinR-HSA-5617492 (Reactome)
HOXB2 active chromatinR-HSA-5621002 (Reactome)
HOXB2 bivalent chromatinR-HSA-6810159 (Reactome)
HOXB2 geneR-HSA-5617486 (Reactome)
HOXB2 mRNAArrowR-HSA-5617486 (Reactome)
HOXB2 mRNAR-HSA-5617485 (Reactome)
HOXB2ArrowR-HSA-5617485 (Reactome)
HOXB3 active chromatinArrowR-HSA-6810158 (Reactome)
HOXB3 active chromatinR-HSA-5617661 (Reactome)
HOXB3 bivalent chromatinR-HSA-6810158 (Reactome)
HOXB3 geneR-HSA-5617672 (Reactome)
HOXB3 mRNAArrowR-HSA-5617672 (Reactome)
HOXB3 mRNAR-HSA-5617668 (Reactome)
HOXB3ArrowR-HSA-5617668 (Reactome)
HOXB3TBarR-HSA-5617454 (Reactome)
HOXB4 geneR-HSA-5617867 (Reactome)
HOXB4 mRNAArrowR-HSA-5617867 (Reactome)
HOXB4 mRNAR-HSA-5617881 (Reactome)
HOXB4ArrowR-HSA-5617881 (Reactome)
HOXC4 active chromatinArrowR-HSA-5617866 (Reactome)
HOXC4 active chromatinArrowR-HSA-5617887 (Reactome)
HOXC4 bivalent chromatinR-HSA-5617887 (Reactome)
HOXC4 geneR-HSA-5617866 (Reactome)
HOXC4 mRNAArrowR-HSA-5617866 (Reactome)
HOXC4 mRNAR-HSA-5617855 (Reactome)
HOXC4ArrowR-HSA-5617855 (Reactome)
HOXD1 active chromatinArrowR-HSA-5617445 (Reactome)
HOXD1 active chromatinArrowR-HSA-5617462 (Reactome)
HOXD1 bivalent chromatinR-HSA-5617445 (Reactome)
HOXD1 geneR-HSA-5617462 (Reactome)
HOXD1 mRNAArrowR-HSA-5617462 (Reactome)
HOXD1 mRNAR-HSA-5617446 (Reactome)
HOXD1ArrowR-HSA-5617446 (Reactome)
HOXD3 active chromatinArrowR-HSA-5617642 (Reactome)
HOXD3 active chromatinArrowR-HSA-5617650 (Reactome)
HOXD3 bivalent chromatinR-HSA-5617650 (Reactome)
HOXD3 geneR-HSA-5617642 (Reactome)
HOXD3 mRNAArrowR-HSA-5617642 (Reactome)
HOXD3 mRNAR-HSA-5617652 (Reactome)
HOXD3ArrowR-HSA-5617652 (Reactome)
HOXD4 geneR-HSA-5617874 (Reactome)
HOXD4 mRNAArrowR-HSA-5617874 (Reactome)
HOXD4 mRNAR-HSA-5617864 (Reactome)
HOXD4ArrowR-HSA-5617864 (Reactome)
JUNR-HSA-5617661 (Reactome)
MAFB,

HOXB1:PBX1:PKNOX1 at active HOXA3

chromatin
ArrowR-HSA-5617641 (Reactome)
MAFB,

HOXB1:PBX1:PKNOX1 at active HOXA3

chromatin
ArrowR-HSA-5617676 (Reactome)
MAFB:JUN and EGR2 at

active HOXB3

chromatin
ArrowR-HSA-5617661 (Reactome)
MAFB:JUN and EGR2 at

active HOXB3

chromatin
ArrowR-HSA-5617672 (Reactome)
MAFBR-HSA-5617641 (Reactome)
MAFBR-HSA-5617661 (Reactome)
MEIS1R-HSA-5693644 (Reactome)
MLL2,3 complexR-HSA-5617431 (Reactome)
MLL2,3 complexR-HSA-5617452 (Reactome)
MLL2,3 complexR-HSA-5617492 (Reactome)
MLL2,3 complexR-HSA-5617859 (Reactome)
MLL2,3 complexR-HSA-5617887 (Reactome)
MLL2,3 complexR-HSA-5617896 (Reactome)
MLL2,3 complexR-HSA-6810139 (Reactome)
MLL2,3 complexR-HSA-6810158 (Reactome)
MLL2,3 complexR-HSA-6810159 (Reactome)
MLL2,3 complexR-HSA-6810161 (Reactome)
MLL2,3 complexmim-catalysisR-HSA-5617431 (Reactome)
MLL2,3 complexmim-catalysisR-HSA-5617887 (Reactome)
NCOA3R-HSA-5617431 (Reactome)
NCOA3R-HSA-5617452 (Reactome)
NCOA3R-HSA-5617859 (Reactome)
NCOA3R-HSA-5617862 (Reactome)
NCOA3R-HSA-5617896 (Reactome)
NCOR1ArrowR-HSA-5617431 (Reactome)
NCOR1ArrowR-HSA-5617452 (Reactome)
NCOR1ArrowR-HSA-5617859 (Reactome)
NCOR1ArrowR-HSA-5617862 (Reactome)
NCOR1ArrowR-HSA-5617896 (Reactome)
PAX6R-HSA-5617896 (Reactome)
PBX1:PKNOX1,MEIS1R-HSA-5621002 (Reactome)
PBX1:PKNOX1R-HSA-5617641 (Reactome)
PBX1:PKNOX1R-HSA-5621010 (Reactome)
PBX1:PKNOX1R-HSA-5693644 (Reactome)
PCGF2ArrowR-HSA-5617896 (Reactome)
PIAS2ArrowR-HSA-5617454 (Reactome)
PRC2 (EZH2) CoreArrowR-HSA-5617431 (Reactome)
PRC2 (EZH2) CoreArrowR-HSA-5617445 (Reactome)
PRC2 (EZH2) CoreArrowR-HSA-5617452 (Reactome)
PRC2 (EZH2) CoreArrowR-HSA-5617650 (Reactome)
PRC2 (EZH2) CoreArrowR-HSA-5617859 (Reactome)
PRC2 (EZH2) CoreArrowR-HSA-5617862 (Reactome)
PRC2 (EZH2) CoreArrowR-HSA-5617887 (Reactome)
PRC2 (EZH2) CoreArrowR-HSA-5617896 (Reactome)
PRC2 (EZH2) CoreArrowR-HSA-6810139 (Reactome)
PRC2 (EZH2) CoreArrowR-HSA-6810158 (Reactome)
PRC2 (EZH2) CoreArrowR-HSA-6810159 (Reactome)
PRC2 (EZH2) CoreArrowR-HSA-6810161 (Reactome)
R-HSA-5617431 (Reactome) As inferred from mouse embryos and cell lines, retinoic acid binds the RARA or RARG receptor in a RAR:RXR dimer bound to the 3' region of HOXA1. Ligand binding by retinoic acid receptors causes dismissal of corepressors such as NCOR1 (Klein et al. 2000), recruitment of coactivators such as NCOA3, and alteration of chromatin at the HOXA1 gene to an active conformation. Similar activation of HOXA1 is also observed in vitro in human breast cancer cells (Chariot et al. 1995). In mouse and Xenopus Hoxa1 acts in a feedback loop to maintain retinoic acid synthesis by directly binding and activating the promoter of the Raldh2 gene.
In addition to recruiting transcription coactivators, retinoic acid also appears to affect histone modifications and DNA methylation. In human embryonal carcinoma cells, KDM6A (UTX) binds the HOXA1 gene upon retinoic acid treatment and demethylates trimethylated lysine-27 of histone H3 (H3K27me3) (Lee et al. 2007). Reduced H3K27me3 is also observed at HOXA1 in lung fibroblasts (Lan et al. 2007). Experiments with mouse embryos lacking Kdm6a and Kdm6b indicate other factors also participate in demethylation of H3K27me3 (Shpargel et al. 2014). Polycomb repressive complex 2 (PRC2), which binds H3K27me3, is also lost during activation by retinoic acid (inferred from mouse cells and also observed in human embryonal carcinoma cells, Lee et al. 2007, Sessa et al. 2007). KDM6A forms complexes with the histone methyltransferases KMT2C,D (MLL2,3) (Lee et al. 2007) which may participate in methylating histone H3 at lysine-4 (H3K4me3), an activating chromatin modification. At the 3' end of the HOXA cluster 5-methylcytosine in CG-rich regions is converted to 5-hydroxymethylcytosine by TET2 during retinoic acid induced differentiation of embryonal carcinoma cells (Bocker et al. 2012). During retinoic acid activation of HOXA genes in human monocytic leukemia cells the HOXA cluster is unfolded and its chromosomal domain is repositioned within the nucleus (Rousseau et al. 2014). Similar large-scale rearrangements may occur during embryogenesis.
In mouse embryos, expression of Hoxa1 occurs in the neural tube, adjacent mesenchyme, paraxial mesoderm, somites, and gut epithelium from rhombomere 4 to the caudal-most region of the embryo. (Rhombomeres are transiently formed segments in the neural tube that will eventually form the hindbrain.)
R-HSA-5617445 (Reactome) As inferred from the Hoxd1 homolog in mouse embryos, HOXD1 is not expressed in hindbrain. In mouse, expression of Hoxd1 begins at E8.5 in caudal lateral mesoderm. At E9.5 to E11.5 Hoxd1 expression is observed in prosomeres p2 and p3 of the diencephalon, dermatomes, urogenital tubercle, and tail bud. Expression is inducible by retinoic acid in neuroblastoma cells, however it is unknown if the induction is direct or indirect (Manohar et al. 1996, Zha et al. 2012). Nerve Growth Factor induces Hoxd1 expression in nociceptors of mouse embryos. As inferred from human posterior HOXD genes in primary human fibroblasts (Lan et al. 2007), other anterior HOX genes, and mouse Hoxd1, the activation of HOXD1 chromatin may be associated with loss of methylation at lysine-27 of histone H3 (H3K27me3) loss of polycomb repressive complex 2 (PRC2), gain of histone acetylation, and gain of methylation at histone H3K4. Like other Hox gene clusters, the HoxD cluster in mouse changes position relative to other loci in the nucleus during activation.
R-HSA-5617446 (Reactome) The HOXD1 mRNA is translated to yield HOXD1 protein.
R-HSA-5617452 (Reactome) As inferred from mouse embryos and cell lines, retinoic acid binds receptors (RARA or RARG) at retinoic acid response elements (RAREs) located 3' to the HOXB1 gene, causing recruitment of coactivators such as NCOA3 and alteration of chromatin at the HOXB1 gene to an active conformation. Similar activation of the HOXB cluster by retinoic acid is observed in human embryonal carcinoma cells (Simeone et al. 1990). In human carcinoma cells and primary fibroblasts, KDM6A (UTX) binds the HOXB1 gene upon retinoic acid treatment (Agger et al. 2007, Lee et al. 2007) and may demethylate trimethylated lysine-27 of histone H3 (H3K27me3). Reduced H3K27me3 is also observed at HOXB1 in lung fibroblasts (Lan et al. 2007). Other demethylases may be redundant with KDM6A. Polycomb repressive complex 2 (PRC2), which binds H3K27me3, is also lost during activation (Lee et al. 2007). KDM6A forms complexes with the histone methyltransferase KMT2C,D (MLL2,3) which may participate in methylating histone H3 at lysine-4 (H3K4me3), an activating chromatin modification (Lee et al. 2007). After activation by retinoic acid HOXB1 maintains its own expression by binding elements in its own promoter and activating expression (Di Rocco et al. 1997).
In mouse embryos, Hoxb1 is expressed in mesoderm and neurectoderm of primitive streak stage embryos and then becomes restricted to rhombomeres of the hindbrain. Before rhombomere formation Hoxb1 is initially expressed in the region that becomes r3-7. After rhombomere formation Hoxb1 becomes restricted to r4 and is also observed in caudal mesoderm. Hoxb1 activates expression of Egr2 (Krox20), a transcription factor that subsequently activates Hoxa2, Hoxb2, and Hoxb3 and represses Hoxb1.
R-HSA-5617454 (Reactome) After activation by retinoic acid, the HOXB1 gene is transcribed to yield mRNA (in embryos in Giampaolo et al. 1989, in human embryonal carcinoma cells in Simeone et al. 1990, Ogura and Evans 1995).
In mouse embryos, Hoxb1 is expressed in mesoderm and neurectoderm of primitive streak stage embryos and then becomes restricted to rhombomeres of the hindbrain. Before rhombomere formation Hoxb1 is initially expressed in the region that becomes r3-7. After rhombomere formation Hoxb1 becomes restricted to r4 and is also observed in caudal mesoderm.
R-HSA-5617457 (Reactome) The HOXB1 mRNA is translated to yield HOXB1 protein. The HOXB1 mRNA is a target of miR-10a (Weiss et al. 2009) and miR-196 (Yekta et al. 2008).
R-HSA-5617458 (Reactome) The HOXA1 mRNA is translated to yield HOXA1 protein (Chen et al. 2013, Chen et al. 2014). MicroRNAs miR-10a (Garzon et al. 2006), let-7c (Zhan et al. 2013), miR-99 (Chen et al. 2013) and miR-100 (Chen et al. 2014) negatively regulate translation in adult cells, however their roles in embryonic cells are unknown.
R-HSA-5617462 (Reactome) The HOXD1 gene is transcribed to yield mRNA (Manohar et al. 1996, Zha et al. 2012). The Hoxd1 homologue in mouse is expressed in caudal lateral mesoderm, prosomeres p2 and p3, dermatomes, urogenital tract, gut endoderm, and tail bud.
R-HSA-5617471 (Reactome) After activation by retinoic acid, the HOXA1 gene is transcribed to yield mRNA (inferred from mouse embryos, also demonstrated in human cancer cells, Chariot et al. 1995, Xu et al. 2014). The mRNA is a target of the microRNAs miR-10a in megakaryocytes (Garzon et al. 2006), miR210 in tumors (Huang et al. 2009), let-7c in non-small cell lung cancer cells (Zhan et al. 2013), miR-99 in epithelial cells (Chen et al. 2013), and miR-100 in tumor cells (Chen et al. 2014), however it is unknown if these play a role in embryogenesis. Opposite strand intergenic transcripts are also observed in adult tissues and placenta (Sessa et al. 2007).
In mouse embryos, expression of Hoxa1 occurs in the neural tube, adjacent mesenchyme, paraxial mesoderm, somites, and gut epithelium from rhombomere 4 to the caudal-most region of the embryo. (Rhombomeres are transiently formed segments in the neural tube that will eventually form the hindbrain.)
R-HSA-5617479 (Reactome) HOXA2 mRNA is translated to yield HOXA2 protein. The microRNA miR-3960 represses translation of HOXA2 (inferred from mouse).
R-HSA-5617483 (Reactome) The HOXA2 is transcribed to yield mRNA (in carcinoma cells, Yates et al. 2010). In mouse embryos Hoxa2 mRNA is observed in rhombomere 2 and caudally through posterior hindbrain, spinal cord, larynx, lungs, vertebrae, sternum, and intestine. Hoxa2 mRNA is a target of microRNA miR-3960 in differentiating mouse osteoblasts.
R-HSA-5617484 (Reactome) As inferred from mouse embryos, HOXA2 expression is directly driven by EGR2 (KROX20) in rhombomeres 3 and 5 (r3, r5) of the hindbrain and by HOXB1 in r4. EGR2 binds sites in the 5' region of the HOXA2 gene. HOXB1 sets up the correct EGR2 expression domain in r3 and thereby indirectly regulates HOXA2 in this region. (HOXA2 is the only HOX gene active in r2. An unknown activator, possibly a transcription factor of the SOX family, may be involved in expression in r2.)
R-HSA-5617485 (Reactome) The HOXB2 mRNA is translated to yield HOXB2 protein (Sengupta et al. 1994, Segara et al. 2005, Zhai et al. 2005).
R-HSA-5617486 (Reactome) The HOXB2 gene is transcribed to yield mRNA (in embryos in Giampaolo et al. 1989, in carcinoma cells in Simeone et al. 1990). In mouse embryos Hoxb2 mRNA is observed in rhombomere 3 and caudally in the neural tube and mesoderm derivatives such as lung.
R-HSA-5617492 (Reactome) As inferrred from mouse embryos, EGR2 (KROX20) binds three sites in the 5' region of the HOXB2 gene and activates expression in rhombomere 3 (r3) and r5. HOXB1 activates HOXB2 in r4 and expression is also observed in r6 and r7.
R-HSA-5617641 (Reactome) As inferred from mouse embryos, the transcription factor MAFB (KREISLER, KMRL) initially activates the HOXA3 gene in rhombomere 5 (r5) and r6. Weaker expression is also observed in r7. HOXA3 autoregulates by binding and activating its own promoter.
R-HSA-5617642 (Reactome) The HOXD3 gene is transcribed to yield mRNA (Zha et al. 2012). In mouse embryos Hoxd3 mRNA is observed in the neural tube with an anterior boundary at the junction of rhombomeres 4-5 and in the dorsal root ganglia, first cervical vertebra, thyroid gland, kidney tubules, esophagus, stomach, and intestines.
R-HSA-5617643 (Reactome) HOXA3 mRNA is translated to yield HOXA3 protein.
R-HSA-5617650 (Reactome) Retinoic acid induces expression of HOXD3 in neuroblastoma cells (Zha et al. 2012) and mouse embryos but it is unknown if the effect is direct or indirect. In mouse embryos the retinoid receptor Rarb is not responsible for the inducibility. As inferred from mouse embryos HOXD3 is expressed in rhombomeres 5, 6, and 7 (r5-7). As inferred from mouse Hoxd3, activation of HOXD3 chromatin is associated with loss of methylation at lysine-27 of histone H3 (H3K27), loss of PRC2, and gain of methylation at H3K4.
R-HSA-5617652 (Reactome) HOXD3 mRNA is translated to yield HOXD3 protein (Zha et al. 2012).
R-HSA-5617661 (Reactome) As inferred from mouse embryos, the MAFB:JUN (KREISLER:JUN) heterodimer binds the rhombomere 5 (r5) enhancer located 5' to the P1 promoter of the HOXB3 gene and activates expression in r5. EGR2 (KROX20) also binds the r5 enhancer is required to activate the HOXB3 gene in r5. After initial activation HOXB3 is hypothesized to maintain its own expression. HOXB3 is expressed most strongly in r5 and more weakly in caudal rhombomeres r6 and r7.
R-HSA-5617668 (Reactome) HOXB3 mRNA is translated to yield HOXB3 protein (Palakurthy et al. 2009, Li et al. 2012, Chen et al. 2013). Translation is repressed by the microRNAs miR-7 and miR-218 (Li et al. 2012) and miR-10A (Weiss et al. 2009).
R-HSA-5617672 (Reactome) The HOXB3 gene is transcribed to yield mRNA (in embryos in Giampaolo et al. 1989, in carcinoma cells in Simeone et al. 1990). The HOXB3 mRNA is a target of the microRNAs miR-7 and miR-218 in breast cancer cells (Li et al. 2012) and miR-10A (Weiss et al. 2009). In mouse embryos Hoxb3 mRNA is observed strongly in rhombomere 5 and more weakly in rhombomeres 6 and 7 of the hindbrain. Hoxb3 mRNA is also observed in mesodermal derivatives including lung, stomach, pancreas, and metanephros, and in neural crest derivatives.
R-HSA-5617676 (Reactome) The HOXA3 gene is transcribed to yield mRNA (Han et al. 2007). In mouse embryos Hoxa3 mRNA is observed in rhombomere 5 and caudally through the central nervous system, ectoderm, and somitic mesoderm. HOXA3 mRNA is a target of the microRNA miR-10a (Han et al. 2007).
R-HSA-5617855 (Reactome) HOXC4 mRNA is translated to yield HOXC4 protein.
R-HSA-5617859 (Reactome) As inferred from mouse embryos, retinoic acid activates the HOXB4 gene in rhombomere 7 (r7) by binding retinoic acid receptor RARB (Folberg et al. 1999) and perhaps RARA in RAR:RXR dimers bound to retinoic acid response elements (RAREs) located in the 3' flanking region of the HOXB4 gene, causing dissociation of corepressors and recruitment of coactivators. HOXB4 maintains its own expression by binding and activating its own promoter.
In human fibroblasts activation of chromatin at the HOXB4 gene accompanied by loss of methylation of lysine-27 at histone H3 (H3K27me3, Lan et al. 2007). Based on observations from mouse embryonic stem cells, Polycomb repressive complex 2 (PRC2), which binds H3K27me3, is anticipated to be lost while methylation of H3K4 is gained, possibly through the action of the histone demethylase KDM6A (UTX) which, in human fibroblasts, binds HOXB4 (Lan et al. 2007). Other factors may be involved in demethylating H3K27me3. KDM6A can form complexes containing the histone methyltransferases KMT2C,D (MLL2,3) which may participate in methylating H3K4 (Lee et al. 2007).
R-HSA-5617862 (Reactome) As inferred from mouse embryos, retinoic acid initially activates expression of the HOXA4 gene in rhombomere 7 (r7) by binding RARB or RARA in dimeric RAR:RXR complexes located at retinoic acid response elements (RAREs) in the 5' flanking region of the HOXA4 promoter (also observed in human teratocarcinoma cells in Doerksen et al. 1996, Sessa et al. 2007), correlating dissociation of corepressors and recruitment of coactivators. In mouse embryos Hoxa4 itself maintains later expression in an autoregulatory loop.
In human fibroblasts (Lan et al. 2007) and teratocarcinoma cells (Sessa et al 2007) activation of HOXA4 chromatin is accompanied by loss of methylation at lysine-27 of histone H3 (H3K27me3) and gain of H3K4me3. The polycomb repressive complex 2 (PRC2), which binds H3K27me3, is also reduced at active HOXA4 chromatin (Lan et al. 2007, Sessa et al. 2007).
R-HSA-5617864 (Reactome) HOXD4 mRNA is translated to yield HOXD4 protein (Zappavigna et al. 1991).
R-HSA-5617866 (Reactome) The HOXC4 gene is transcribed to yield mRNA. In mouse embryos Hoxc4 mRNA is observed caudal to rhombomere 7 in spinal column, prevertebrae, esophagus, metanephric kidney, lung, and trachea.
R-HSA-5617867 (Reactome) The HOXB4 gene is transcribed to yield mRNA (in embryos in Giampaolo et al. 1989, in carcinoma cells in Simeone et al. 1990). The microRNA miR-23a binds the 3' untranslated region of HOXB4 mRNA (Koller et al 2013). In mouse embryos Hoxb4 mRNA is observed in rhombomere 7, paraxial mesoderm of somite 7, and caudally.
R-HSA-5617874 (Reactome) The HOXD4 gene is transcribed to yield mRNA (Moroni et al. 1993, Morrison et al. 1996, Morrison et al. 1997). In mouse embryos Hoxd4 mRNA is observed in rhombomere 7 and caudally in spinal cord and prevertebrae. The HOXD4 promoter region is a target of the microRNA miR-10a, which causes repression of transcription (Tan et al. 2009).
R-HSA-5617877 (Reactome) The HOXA4 gene is transcribed to yield mRNA (Doerksen et al. 1996). In mouse cells, microRNAs miR-196a-2, miR-196b, and miRNA miR-222 target Hoxa4 mRNA untranslated regions. In mouse embryos Hoxa4 mRNA is observed in rhombomere 7, mesoderm (including somites, lung, and kidney), rostral-dorsal stomach, rostral prececal gut, and large intestine.
R-HSA-5617879 (Reactome) The HOXA4 mRNA is translated to yield HOXA4 protein. In mouse cells the microRNAs miR-196a-2, miR-196b, and miR-222 repress expression of Hoxa4.
R-HSA-5617881 (Reactome) HOXB4 mRNA is translated to yield HOXB4 protein. Protein expression is repressed by miR-23a (Koller et al. 2013).
R-HSA-5617887 (Reactome) As inferred from mouse embryos, HOXC4 is expressed at E12.5 caudal to rhombomere 7 (r7) and at the level of prevertebrae 4-5 and caudally. In carcinoma cells treated with retinoic acid (Lee et al. 2007) and primary fibroblasts (Lan et al. 2007) chromatin at HOXC4 loses methylation at lysine-27 of histone H3 (H3K27me3), loses polycomb repressive complex 2 (PRC2), and gains methylation at lysine-4 of histone H3 (H3K4me3). In embryonal carcinoma cells KDM6A (UTX) binds HOXC4 and participates in demethylating H3K27 at HOXC4 (Lee et al. 2007)
R-HSA-5617896 (Reactome) As inferred from mouse embryos, retinoic acid activates the HOXD4 gene in rhombomere 7 (r7) by binding RARB or RARA in RAR:RXR receptor dimers bound to a retinoic acid response element (RAREs) in the 5' flanking region of the gene. Ligand binding by retinoic acid receptors causes dismissal of corepressors such as NCOR1 and recruitment of coactivators such as NCOA3 (Klein et al. 2000). The response of HOXD4 to retinoic acid is also observed in human embryonal carcinoma cells (Moroni et al. 1993, Morrison et al. 1996, Morrison et al. 1997). PAX6 binds near the RARE and is required for maximal activation.
In human fibroblasts chromatin at HOXA genes is activated by loss of methylation at lysine-27 (H3K27me3), loss of Polycomb repressive complex 2 (PRC2), and gain of H3K4me3 (Lan et al. 2007). Similar changes occur at Hoxd4 in mouse embryos. The histone demethylase KDM6A (UTX) binds the HOXD4 gene in human lung fibroblasts and may participate in demethylating H3K27me3 (Lan et al. 2007). Other factors may also be involved in demethylation. KDM6A associates with the histone methyltransferases KMT2C,D (MLL2,3) which may participate in methylating H3K4 (Lee et al. 2007). As inferred from mouse homologs, PCGF2 (MEL18) dissociates from Hoxd4 during activation. After activation by retinoic acid, HOXD4 maintains its own expression by binding and activating its own promoter.
R-HSA-5621002 (Reactome) As inferred from mouse embryos, HOXB1 in a trimeric complex with PBX1 and MEIS1 or PKNOX1 (PREP1) binds an enhancer located 5' to the HOXB2 gene and activates expression of HOXB2 in rhombomere 4 (r4). EGR2 (KROX20) activates HOXB2 in r3 and r5 and expression is also observed in r6 and r7.
R-HSA-5621010 (Reactome) As inferred from mouse homologs, HOXA2 expression is driven by HOXB1 in rhombomere 4 (r4) and EGR2 (KROX20) in r3 and r5. HOXB1 together with PBX and PREP/MEIS cofactors bind an element in the intron of HOXA2. (HOXA2 is the only HOX gene active in r2. An unknown activator, possibly a transcription factor of the SOX family, may be involved in expression in r2.)
R-HSA-5693644 (Reactome) As inferred from mouse embryos and embryonal carcinoma cells, HOXB1 binds with the PBX1:PKNOX1 (PBX1:PREP1) heterodimer (Berthelsen et al. 1998) and MEIS1at the promoter of the HOXB1 gene to maintain expression after initial activation of HOXB1 by retinoic acid signaling. Binding of SOX:OCT heterodimers to the mouse HOXB1 promoter also appear to positively regulate HOXB1 transcription.
R-HSA-6810139 (Reactome) In human cell lines and tissues activation of HOXA2 chromatin by retinoic acid occurs through loss of methylation at lysine-27 of histone H3 (H3K27), dissociation of polycomb repressive complexes, and gain of methylation at H3K4 (Lee et al. 2007 Supplementary, Sakamoto et al. 2007, Sessa et al. 2007). The change in chromatin may be produced by euchromatin spreading from distant 3' retinoic acid response elements. DNA methylation and MBD1 also appear to play a role in maintaining repression at HOXA2 in HeLa cells (Sakamoto et al. 2007). The histone demethylase KDM6A binds HOXA2 (Lee et al. 2007 Supplementary) and may participate in removing H3K27 methylation. KDM6A associates with histone methyltransferases KMT2C,D (MLL2,3) which may participate in methylating H3K4 in embryonal carcinoma cells (Lee et al. 2007, also observed at other HOXA genes in Lan et al. 2007). The conformation of the entire HOXA cluster in the nucleus changes during differentiation of a myeloid leukemia cell line and the conformation changes correlate with gene activity, H3K27me2,3 occurence, and proximity to CTCF binding sites (Rousseau et al. 2014, see also Lonfat and Duboule 2015).
R-HSA-6810158 (Reactome) During activation of HOXB3 by retimoic acid in fibroblasts (Lan et al. 2007) and embryonal carcinoma cells (Lee et al. 2007) chromatin at HOXB3 loses methylation at lysine-27 of histone H3 (H3K27me3), loses PRC2, and gains methylation at H3K4. The demethylase KDM6A (UTX) binds HOXB3 chromatin during activation (Lan et al. 2007, Lee et al. 2007) and may participate in demethylating H3K27me3. KDM6A forms complexes with the histone methyltransferases KMT2C,D (MLL2,3) which may participate in methylating H3K4 (Lee et al. 2007)
R-HSA-6810159 (Reactome) During activation of HOXB1 by retinoic acid in human embryonal carcinoma cells, methylation at lysine-27 of histone H3 (H3K27me3) is lost and methylation at lysine-4 (H3K4me3) is gained (Lan et al. 2007, Lee et al. 2007). The histone demethylase KDM6A (UTX) binds HOXB2 chromatin and may demethylate H3K27me3 (Lee et al. 2007). Other factors may also participate in demethylation. Loss of H3K27me3 is associated with loss of polycomb repressive complex 2 (PRC2) (Lan et al. 2007, Lee et al. 2007). KDM6A forms complexes with the histone methyltransferases KMT2C,D (MLL2,3) which may participate in methylating H3K4 (Lee et al. 2007). The activation of HOXB1 chromatin may be produced by euchromatin spreading from distant 3' retinoic acid response elements.
R-HSA-6810161 (Reactome) In human fibroblasts (Lan et al. 2007) and human embryonic carcinoma cells (Lee et al. 2007, Sessa et al. 2007) treated with retinoic acid HOXA3 chromatin is activated by loss of methylation at lysine-27 of histone H3 (H3K27me3) and gain of H3K4me3. KDM6A (UTX) binds near HOXA3 (Lan et al. 2007, Lee et al. 2007) but does not appear to participate in the loss of H3K27me3. KDM6A forms complexes with the histone methyltransferases KMT2C,D (MLL2,3) which may participate in methylating H3K4 (Lee et al. 2007). Polycomb repressive complex 2 (PRC2), which binds H3K27me3, is also lost during activation of HOXA3 (Lan et al. 2007, Lee et al. 2007, Sessa et al. 2007). The change in chromatin at HOXA3 may result from euchromatin spreading from distant 3' retinoic acid response elements. The chromosomal conformation of the entire HOXA cluster changes during activation (Rousseau et al. 2014).
RARA,B:RXRA at HOXA4 bivalent chromatinR-HSA-5617862 (Reactome)
RARA,B:RXRA at HOXB4 bivalent chromatinR-HSA-5617859 (Reactome)
RARA,B:RXRA at HOXD4 bivalent chromatinR-HSA-5617896 (Reactome)
RARA,G:RXRA at HOXA1 bivalent chromatinR-HSA-5617431 (Reactome)
RARA,G:RXRA at HOXB1 bivalent chromatinR-HSA-5617452 (Reactome)
RNA Polymerase II

holoenzyme complex

(generic)
R-HSA-5617431 (Reactome)
RNA Polymerase II

holoenzyme complex

(generic)
R-HSA-5617445 (Reactome)
RNA Polymerase II

holoenzyme complex

(generic)
R-HSA-5617452 (Reactome)
RNA Polymerase II

holoenzyme complex

(generic)
R-HSA-5617484 (Reactome)
RNA Polymerase II

holoenzyme complex

(generic)
R-HSA-5617492 (Reactome)
RNA Polymerase II

holoenzyme complex

(generic)
R-HSA-5617641 (Reactome)
RNA Polymerase II

holoenzyme complex

(generic)
R-HSA-5617650 (Reactome)
RNA Polymerase II

holoenzyme complex

(generic)
R-HSA-5617859 (Reactome)
RNA Polymerase II

holoenzyme complex

(generic)
R-HSA-5617862 (Reactome)
RNA Polymerase II

holoenzyme complex

(generic)
R-HSA-5617887 (Reactome)
RNA Polymerase II

holoenzyme complex

(generic)
R-HSA-5617896 (Reactome)
RNA Polymerase II

holoenzyme complex

(generic)
R-HSA-5621002 (Reactome)
RNA Polymerase II

holoenzyme complex

(generic)
R-HSA-5621010 (Reactome)
RQCD1ArrowR-HSA-5617471 (Reactome)
atRA:RARA,B:RXRA at

active HOXA4

chromatin
ArrowR-HSA-5617862 (Reactome)
atRA:RARA,B:RXRA at

active HOXA4

chromatin
ArrowR-HSA-5617877 (Reactome)
atRA:RARA,B:RXRA at

active HOXB4

chromatin
ArrowR-HSA-5617859 (Reactome)
atRA:RARA,B:RXRA at

active HOXB4

chromatin
ArrowR-HSA-5617867 (Reactome)
atRA:RARA,B:RXRA at

active HOXD4

chromatin
ArrowR-HSA-5617874 (Reactome)
atRA:RARA,B:RXRA at

active HOXD4

chromatin
ArrowR-HSA-5617896 (Reactome)
atRA:RARA,G:RXRA at

active HOXA1

chromatin
ArrowR-HSA-5617431 (Reactome)
atRA:RARA,G:RXRA at

active HOXA1

chromatin
ArrowR-HSA-5617471 (Reactome)
atRA:RARA,G:RXRA at

active HOXB1

chromatin
ArrowR-HSA-5617452 (Reactome)
atRA:RARA,G:RXRA at

active HOXB1

chromatin
ArrowR-HSA-5617454 (Reactome)
atRA:RARA,G:RXRA at

active HOXB1

chromatin
R-HSA-5693644 (Reactome)
atRAArrowR-HSA-5617445 (Reactome)
atRAArrowR-HSA-5617650 (Reactome)
atRAArrowR-HSA-6810139 (Reactome)
atRAArrowR-HSA-6810159 (Reactome)
atRAR-HSA-5617431 (Reactome)
atRAR-HSA-5617452 (Reactome)
atRAR-HSA-5617859 (Reactome)
atRAR-HSA-5617862 (Reactome)
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