RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (Homo sapiens)

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7, 12, 14, 15, 20...2241152120221524151515, 20, 33, 35, 445, 15, 202415, 20, 33, 35, 4415, 20, 345, 1515, 2015, 34393915211515, 20, 33-35, 4415, 201515, 19, 2020, 3841515, 20, 33, 35, 445, 15, 205, 15platelet alpha granule lumennucleoplasmcytosolHIST2H2AC H3K4me2-Nucleosome:ITGA2B gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BHIST1H2BA EP300KAT2B HIST1H4 HIST1H2BL HIST2H2BE KMT2A RUNX1:CBFB:PF4 geneMIR27A gene Me3K5-HIST2H3A KMT2B DPY30 KAT2B HIST2H2AA3 PRKCQRUNX1:CBFB:MYL9 geneRUNX1 H2BFS HIST1H2BM KMT2B KMT2D HIST1H2AJ PRMT1 MIR27A geneSIN3A H2BFS H2AFB1 NFE2HIST1H2BM HIST1H2BO KAT2B HIST1H2BN HIST1H2BJ MeR206,MeR210-RUNX1 HIST3H2BB PF4 geneHIST1H2AB PRMT1 HIST1H2BN H2AFZ MIR27A gene WDR5 HIST1H2BJ HIST2H2AA3 RUNX1:CBFB:NR4A3geneSIN3B KMT2A HIST2H2BE HIST1H2BD SETD1A HIST2H2AC KAT2B EIF2C1 SETD1A H2AFX HIST1H2AC Me2K5-HIST2H3A PRKCQ geneHIST1H2AB H2AFV HIST1H2BA H2AFB1 RBBP5 Me2K5,Me2aR2-H3F3A HIST1H2BD CBFB EP300 HIST1H2AD HIST1H2BN HIST3H2BB ZFPM1 HIST1H2AC Me2K5-H3F3A EP300 THBS1 HIST3H2BB SIN3B GATA1 HIST2H2AA3 Me2K5-HIST2H3A PF4 gene AdoMetHIST1H2AJ Me3K5-HIST2H3A H2AFZ GATA1 H2AFZ HIST1H2BD HIST1H2BL HIST1H2BA HIST1H2BK HIST2H2AA3 HIST1H2AD EP300 PRMT1 HIST1H2BH Me2K5-HIST1H3A PRKCQ gene H2AFZ HIST1H2BH KMT2E HIST1H2AC CBFB SIN3A WDR5 HIST1H2BH H2AFX KMT2A SETD1A MeR206,MeR210-RUNX1 CBFB H2AFZ H2BFS HIST1H2BC KMT2A HIST1H2BC H3K4me3-Nucleosome:MIR27A gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BH2AFZ Me2K5-HIST1H3A H2AFZ HIST1H2BK Me2K5-HIST2H3A KMT2B ASH2L ZFPM1 Me3K5-H3F3A HIST1H2BL SETD1B HIST1H2AD SIN3B HIST1H2BN HIST3H2BB H2AFJ HIST1H2BA PRMT6HIST1H2BJ HIST1H2BM H2AFV KMT2A CBFB HIST1H2BB HIST1H2BA CBFB Regulation of RUNX1Expression andActivityHIST3H2BB KMT2B HIST1H2BL THBS1 gene HIST1H2BK Me2K5-HIST2H3A H2AFB1 DPY30 HIST2H2AA3 SIN3A SETD1A HDAC1 H2AFB1 KMT2E Me2K5,Me2aR3-HIST1H3A HIST1H2AB HIST2H2BE HIST1H2BH EP300 H2AFZ KMT2C RBBP5 HIST1H2BB HIST1H2BK PRMT6 H2AFZ H2AFJ PRMT1 CBFB HIST1H2BO MIR27A gene RUNX1 HIST1H2BO H2BFS SETD1B HIST1H2BJ HIST1H4 H2AFJ MeR206,MeR210-RUNX1 H2AFX HIST1H2AC HIST1H2BK HIST2H2BE HIST2H2AC GATA1 HIST1H2BO RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1Me2K5-HIST2H3A TNRC6C HIST1H2BA HIST1H2BM H2AFX NR4A3HIST2H2AC HIST1H2BB RUNX1:CBFB:SIN3A(SIN3B):PRMT6:HDAC1Me2K5,Me2aR2-H3F3A HIST2H2AA3 HIST1H2BA H2AFV RUNX1 HIST1H2BO RUNX1 EP300 HIST1H2BM H2AFJ Me3K5-H3F3A THBS1 gene CBFB HIST1H2AJ DPY30 HIST1H2BC PRMT6 HIST1H2BA HIST2H2BE SETD1B PRMT1 CBFB CBFB THBS1 gene RUNX1 H2AFV MeR206,MeR210-RUNX1 HIST1H2AC HIST1H2BN MeR206,MeR210-RUNX1 HDAC1 HIST1H2BH KMT2C Me2K5-HIST2H3A SETD1A Me2K5-HIST1H3A KMT2B HIST1H2BN HDAC1 RUNX1 Me3K5-H3F3A HIST1H2BJ HIST1H2AJ H2AFZ Me2K5,Me2aR3-HIST2H3A H2AFB1 HIST2H2BE HIST2H2BE HIST1H2BA HIST1H2AC HIST1H2BN miR-27a H2AFB1 HIST1H2BD H2AFX SIN3B H2AFJ RBBP5 HIST1H2AB TNRC6B RUNX1 HIST1H2AD KMT2D SIN3A NFE2 geneWDR5 Me2K5,Me2aR3-HIST1H3A H2AFV HIST1H2BC HIST2H2AC HIST1H2BM RUNX1 H2AFX HIST2H2AA3 PRMT6 HIST1H4 HIST1H2BK MIR27A gene H2AFJ HIST1H2BL GATA1 DPY30 HIST2H2BE CBFB Me2K5-HIST2H3A HIST1H2BJ HIST1H2BC KMT2C Me2K5-HIST1H3A HIST1H2BN HIST1H2BD HIST2H2BE HIST2H2BE HIST1H4 HIST2H2AC HIST2H2AC DPY30 RUNX1 HIST1H2AC NFE2 gene H2AFJ RUNX1 EIF2C4 THBS1 gene H2BFS HIST1H2BM HIST1H2BC Me3K5-HIST1H3A HIST1H2BD HIST1H2BO KMT2D HIST1H2AC KMT2B HIST1H4 Core MLL complexHIST1H2AD HIST1H2BB EIF2C3 ASH2L MeR206,MeR210-RUNX1 TNRC6A CBFB ZFPM1 HIST1H2AD MeR206,MeR210-RUNX1 HIST1H2BB Me2K5,Me2aR3-HIST2H3A HIST1H2BB HIST1H2BJ HIST1H2AB H2BFS HIST2H2BE HIST1H2BD HIST1H2BM HIST1H2BO HIST1H2AJ EP300 HIST3H2BB HIST1H2BL HIST1H2BB HIST3H2BB H2AFB1 NR4A3 geneCBFB RUNX1 NR4A3 gene Me2K5-H3F3A Me2K5,Me2aR3-HIST1H3A HIST1H2AJ HIST1H2BN RBBP5 ITGA2B(32-1039)HIST1H2BD DPY30 GP1BA gene Me2K5-H3F3A CBFB HIST1H2AC CBFB HIST1H4 AdoHcyH2AFB1 H2AFV HIST2H2BE HIST1H2BD HIST2H2AC GATA1 Me2K5-H3F3A HIST1H4 PRMT1 GP1BARUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:GP1BA gene:H3K4me2,H3R2me2a-NucleosomeGATA1 GATA1:ZFPM1HIST1H2BM RBBP5 SIN3B THBS1 geneHIST1H4 HIST1H2BL HIST1H2AJ HIST1H2BO HIST1H2BB HIST1H2BD H2AFB1 CBFB H2AFV Me2K5,Me2aR2-H3F3A H2AFV HDAC1 HIST1H2BM KMT2C HIST1H2BA H2AFX HIST1H2AD HIST2H2AA3 THBS1 trimerHIST1H2BD KMT2C HIST1H2BC RUNX1 HDAC1 HIST1H2BO HIST1H2AB H2AFJ Me2K5-H3F3A HIST1H2BJ HIST1H2AB ASH2L KMT2C HIST2H2AC H2AFX HIST1H2AD HIST1H2BA HIST1H2BJ CBFB KMT2D ASH2L RUNX1 WDR5 KMT2B CBFB HIST1H2AB MYL9 gene HIST1H2BC PRMT6 H2AFV H2AFJ H3K4me2-Nucleosome:GP1BA gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BPRMT1 HIST1H4 KMT2E HIST2H2AC SIN3A SETD1B H2AFV RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:MIR27A gene:H3K4me2-NucleosomeHIST1H2BJ SETD1A HIST1H2BD EP300 HIST1H2BH WDR5 HIST1H2BK HIST3H2BB H2AFV HIST1H4 HIST2H2AA3 HIST1H2BK AdoMetHIST1H2BK PRMT1 H2AFX RUNX1 miR-27aNonendonucleolyticRISCKMT2B HIST1H2BM ZFPM1 H2AFJ PRMT6 HIST1H2AC HIST1H2BB HIST3H2BB H2AFB1 H2AFB1 H2AFV H3K4me3-Nucleosome:GP1BA gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BSETD1B H2AFZ HIST1H2BA KMT2A HIST1H2BD HIST1H2BB HIST2H2BE HIST1H2BL HIST1H2AB RBBP5 RUNX1:CBFB:PRKCQgeneHIST1H2AD KMT2E HIST1H2BL HIST1H2BB HIST2H2AA3 H2BFS Me2K5-HIST1H3A HIST1H2AB H2BFS GP1BA geneH2AFZ HIST1H2AD HIST1H2AB Me3K5-HIST1H3A HIST1H2BM RUNX1 RUNX1 HIST1H2BO PRMT6 HIST1H2AD H2AFJ HIST2H2BE HIST1H2BH KMT2B SIN3A H2AFJ MOV10 HIST1H2AJ HIST3H2BB H2AFZ KMT2A DPY30 Nucleosome withH3K4me2CBFB Me2K5-HIST2H3A H2AFZ ASH2L KMT2E CBFB HIST1H2BB WDR5 CBFB H2BFS GP1BA gene H2AFX HIST1H2BC HIST1H2BJ ZFPM1 WDR5 HIST2H2BE SIN3B HIST1H2BB HIST1H2AJ RBBP5 HDAC1 MeR206,MeR210-RUNX1 HIST1H2BD H2AFX H2BFS HIST2H2AC HIST1H2AB HIST1H2BK RBBP5 KMT2E HIST1H2BC HIST1H2BN HIST1H2BC HIST1H2AJ HIST1H2BM HIST1H2BO KAT2BHIST1H2AC HIST2H2AC H2AFV HIST1H2BJ H2AFB1 KMT2D RUNX1 HIST1H2BH HIST1H2BO HIST1H2BN Me3K5-H3F3A SETD1A HIST1H4 HIST1H2BA HIST1H2BC H2AFJ HIST3H2BB HIST1H2BL HIST1H2BO PF4(48-101) HIST1H2AD HIST1H2AD HIST1H4 HIST1H2BJ HIST1H2AB HIST2H2BE HIST1H2BK KMT2C ASH2L HIST1H2BK H2BFS KMT2D GP1BA gene HIST2H2AA3 ITGA2B gene H2BFS ASH2L H2AFX RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:THBS1B gene:H3K4me2,H3R2me2a-NucleosomeHIST1H2BO HIST1H2BN SIN3A RUNX1 H2AFB1 RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:MIR27A gene:H3K4me2,H3R2me2a-NucleosomeMe3K5-HIST2H3A SIN3B H2BFS HIST2H2AC HIST1H2BC HIST1H2AJ PRMT6 DPY30 H2AFB1 DPY30 H2AFJ H2AFX KMT2C CBFB RBBP5 Me3K5-HIST1H3A HIST2H2BE HIST1H2BN HIST1H2BH MYL9HIST1H2BN HIST1H2AD ITGA2B geneMe2K5-H3F3A HIST1H2BK HIST1H2BH MeR206,MeR210-RUNX1 H2AFX HIST1H2BH RUNX1 Me2K5,Me2aR3-HIST2H3A H2BFS HIST1H2AB GATA1 HIST1H2BM HIST2H2AC WDR5 Me2K5,Me2aR2-H3F3A GP1BA gene CBFB HIST1H2BB HIST1H2BH HIST1H2AJ Me2K5-H3F3A H3K4me3-Nucleosome:ITGA2B gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BH2AFV HIST1H2AC SETD1B HIST1H2BL H2AFB1 HIST3H2BB HIST1H2BH HIST1H2BM HIST1H2BB H2AFZ HIST1H2BA HIST1H2AC HIST1H4 HIST1H2BL SIN3B RUNX1 RUNX1:CBFBHIST1H4 AdoHcyHIST2H2AA3 EP300 KMT2E PRMT6 HIST1H2BH SIN3A RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:ITGA2B gene:H3K4me2-NucleosomeWDR5 SIN3B HIST1H2BH H2AFV HIST2H2AA3 PF4(32-101) HIST1H2BC H2BFS HIST1H2BJ ASH2L SETD1B HIST1H4 CBFB HIST1H4 HIST2H2AA3 HIST1H2AD HIST1H2BD PRMT1AdoMetSIN3B H2AFX HDAC1 HIST1H2BK HIST3H2BB HIST1H2BO GATA1 Me2K5-H3F3A HIST1H2BL PRMT1 HIST1H2BJ Me3K5-HIST1H3A HIST1H2BC HIST1H2AJ H2AFZ HIST1H2AJ HIST2H2AC HIST1H2BJ HIST1H2AJ KMT2D KAT2B HIST1H2BA KMT2C RUNX1 KMT2D HIST1H2BM Me2K5-HIST1H3A PRMT6 H2AFB1 Me2K5,Me2aR3-HIST2H3A HIST1H2AC CBFB PF4HIST1H2AB HIST1H2BN KMT2A H2AFJ HIST1H2BK RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:ITGA2B gene:H3K4me2,H3R2me2a-NucleosomeHIST1H2BJ HIST1H2BB SETD1B HIST3H2BB HIST1H2BA HIST2H2AA3 H2AFV HIST1H2BA Me3K5-HIST2H3A HIST1H4 HIST1H2BN HIST1H2AD SETD1B GATA1 HIST1H2BL HIST1H2BH HIST1H2AC KAT2B KMT2E HIST1H2BH HIST1H2BL KMT2D ZFPM1 H2BFS HIST1H2BC HIST3H2BB HDAC1 H2AFJ KMT2A HIST1H2AB HIST1H2BN RUNX1 RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:THBS1 gene:H3K4me2-NucleosomeZFPM1 ZFPM1 HIST1H2BD Me2K5-HIST2H3A Me2K5,Me2aR3-HIST1H3A CBFB Me2K5-HIST1H3A HIST1H2BO H2AFX Me2K5-H3F3A HDAC1 MeR206,MeR210-RUNX1 RUNX1:CBFB:PRMT1PRMT1 H2AFJ RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:GP1BA gene:H3K4me2-NucleosomeHIST1H2BK ITGA2B gene HIST1H2AJ HIST1H2BL Me2K5-HIST1H3A KAT2B KAT2B HIST1H2BB HIST2H2AC SIN3A ITGA2B gene H2BFS SETD1A HIST3H2BB HIST1H2BC KMT2E HIST3H2BB HIST1H2BL CBFB HIST2H2AA3 MYL9 geneHIST2H2AA3 HIST1H2AJ HIST1H2AD ASH2L H2AFV RUNX1 SIN3A,(SIN3B)RUNX1 ITGA2B gene RUNX1:CBFB:NFE2 geneMeR206,MeR210-RUNX1:CBFB:PRMT1ZFPM1 HDAC1H3K4me2-Nucleosome:THBS1 gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BH2AFB1 HIST2H2AC PRMT1 H3K4me2-Nucleosome:MIR27A gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BHIST1H2AC SIN3A HIST1H2AB RUNX1 HIST1H2AC AdoHcyH2AFZ HIST1H2BD H2AFX SETD1A HIST1H2BK HIST1H2BM H3K4me3-Nucleosome:THBS1 gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BHIST1H2BO Me2K5-HIST1H3A 15, 192015151515, 2015214424221520392615151515, 201515, 202015, 201-4, 6, 8...4115


Description

In human hematopoietic progenitors, RUNX1 and its partner CBFB are up-regulated at the onset of megakaryocytic differentiation and down-regulated at the onset of erythroid differentiation. The complex of RUNX1 and CBFB cooperates with the transcription factor GATA1 in the transactivation of megakaryocyte-specific genes. In addition, RUNX1 and GATA1 physically interact (Elagib et al. 2003), and this interaction involves the zinc finger domain of GATA1 (Xu et al. 2006). Other components of the RUNX1:CBFB activating complex at megakaryocytic promoters are GATA1 heterodimerization partner, ZFPM1 (FOG1), histone acetyltransferases EP300 (p300) and KAT2B (PCAF), the WDR5-containing histone methyltransferase MLL complex and the arginine methyltransferase PRMT1 (Herglotz et al. 2013). In the absence of PRMT1, the transcriptional repressor complex can form at megakaryocytic promoters, as RUNX1 that is not arginine methylated can bind to SIN3A/SIN3B co-repressors (Zhao et al. 2008). Besides SIN3A/SIN3B, the RUNX1:CBFB repressor complex at megakaryocytic promoters also includes histone deacetylase HDAC1 and histone arginine methyltransferase PRMT6 (Herglotz et al. 2013).
Megakaryocytic promoters regulated by the described RUNX1:CBFB activating and repressing complexes include ITGA2B, GP1BA, THBS1 and MIR27A (Herglotz et al. 2013). ITGA2B is only expressed in maturing megakaryocytes and platelets and is involved in platelet aggregation (Block and Poncz 1995). GP1BA is expressed at the cell surface membrane of maturing megakaryocytes and platelets and participates in formation of platelet plugs (Cauwenberghs et al. 2000, Jilma-Stohlawetz et al. 2003, Debili et al. 1990). THBS1 homotrimers contribute to stabilization of the platelet aggregate (Bonnefoy and Hoylaerts 2008). MIR27A is a negative regulator of RUNX1 mRNA translation and may be involved in erythroid/megakaryocytic lineage determination (Ben-Ami et al. 2009).
The RUNX1:CBFB complex stimulates transcription of the PF4 gene, encoding a component of platelet alpha granules (Aneja et al. 2011), the NR4A3 gene, associated with the familial platelet disorder (FPD) (Bluteau et al. 2011), the PRKCQ gene, associated with inherited thrombocytopenia (Jalagadugula et al. 2011), the MYL9 gene, involved in thrombopoiesis (Jalagadugula et al. 2010), and the NFE2 gene, a regulator of erythroid and megakaryocytic maturation and differentiation (Wang et al. 2010). View original pathway at:Reactome.

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Pathway is converted from Reactome ID: 8936459
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Reactome Author: Orlic-Milacic, Marija

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  30. Hoverter NP, Ting JH, Sundaresh S, Baldi P, Waterman ML.; ''A WNT/p21 circuit directed by the C-clamp, a sequence-specific DNA binding domain in TCFs.''; PubMed Europe PMC Scholia
  31. Freson K, Thys C, Wittewrongel C, Vermylen J, Hoylaerts MF, Van Geet C.; ''Molecular cloning and characterization of the GATA1 cofactor human FOG1 and assessment of its binding to GATA1 proteins carrying D218 substitutions.''; PubMed Europe PMC Scholia
  32. Mizutani S, Yoshida T, Zhao X, Nimer SD, Taniwaki M, Okuda T.; ''Loss of RUNX1/AML1 arginine-methylation impairs peripheral T cell homeostasis.''; PubMed Europe PMC Scholia
  33. Bluteau D, Gilles L, Hilpert M, Antony-Debré I, James C, Debili N, Camara-Clayette V, Wagner-Ballon O, Cordette-Lagarde V, Robert T, Ripoche H, Gonin P, Swierczek S, Prchal J, Vainchenker W, Favier R, Raslova H.; ''Down-regulation of the RUNX1-target gene NR4A3 contributes to hematopoiesis deregulation in familial platelet disorder/acute myelogenous leukemia.''; PubMed Europe PMC Scholia
  34. Wang W, Schwemmers S, Hexner EO, Pahl HL.; ''AML1 is overexpressed in patients with myeloproliferative neoplasms and mediates JAK2V617F-independent overexpression of NF-E2.''; PubMed Europe PMC Scholia
  35. Komeno Y, Yan M, Matsuura S, Lam K, Lo MC, Huang YJ, Tenen DG, Downing JR, Zhang DE.; ''Runx1 exon 6-related alternative splicing isoforms differentially regulate hematopoiesis in mice.''; PubMed Europe PMC Scholia
  36. Xu G, Kanezaki R, Toki T, Watanabe S, Takahashi Y, Terui K, Kitabayashi I, Ito E.; ''Physical association of the patient-specific GATA1 mutants with RUNX1 in acute megakaryoblastic leukemia accompanying Down syndrome.''; PubMed Europe PMC Scholia
  37. Elagib KE, Racke FK, Mogass M, Khetawat R, Delehanty LL, Goldfarb AN.; ''RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation.''; PubMed Europe PMC Scholia
  38. Zhao X, Jankovic V, Gural A, Huang G, Pardanani A, Menendez S, Zhang J, Dunne R, Xiao A, Erdjument-Bromage H, Allis CD, Tempst P, Nimer SD.; ''Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity.''; PubMed Europe PMC Scholia
  39. Lutterbach B, Westendorf JJ, Linggi B, Isaac S, Seto E, Hiebert SW.; ''A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia.''; PubMed Europe PMC Scholia
  40. Bonnefoy A, Hoylaerts MF.; ''Thrombospondin-1 in von Willebrand factor function.''; PubMed Europe PMC Scholia
  41. Sroczynska P, Lancrin C, Kouskoff V, Lacaud G.; ''The differential activities of Runx1 promoters define milestones during embryonic hematopoiesis.''; PubMed Europe PMC Scholia
  42. Browne G, Dragon JA, Hong D, Messier TL, Gordon JA, Farina NH, Boyd JR, VanOudenhove JJ, Perez AW, Zaidi SK, Stein JL, Stein GS, Lian JB.; ''MicroRNA-378-mediated suppression of Runx1 alleviates the aggressive phenotype of triple-negative MDA-MB-231 human breast cancer cells.''; PubMed Europe PMC Scholia
  43. Friedman AD.; ''Cell cycle and developmental control of hematopoiesis by Runx1.''; PubMed Europe PMC Scholia
  44. Aneja K, Jalagadugula G, Mao G, Singh A, Rao AK.; ''Mechanism of platelet factor 4 (PF4) deficiency with RUNX1 haplodeficiency: RUNX1 is a transcriptional regulator of PF4.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114699view16:17, 25 January 2021ReactomeTeamReactome version 75
113144view11:20, 2 November 2020ReactomeTeamReactome version 74
112374view15:30, 9 October 2020ReactomeTeamReactome version 73
101277view11:16, 1 November 2018ReactomeTeamreactome version 66
100814view20:46, 31 October 2018ReactomeTeamreactome version 65
100355view19:22, 31 October 2018ReactomeTeamreactome version 64
99900view16:05, 31 October 2018ReactomeTeamreactome version 63
99457view14:38, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93676view11:30, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ASH2L ProteinQ9UBL3 (Uniprot-TrEMBL)
AdoHcyMetaboliteCHEBI:16680 (ChEBI)
AdoMetMetaboliteCHEBI:15414 (ChEBI)
CBFB ProteinQ13951 (Uniprot-TrEMBL)
Core MLL complexComplexR-HSA-5244738 (Reactome)
DPY30 ProteinQ9C005 (Uniprot-TrEMBL)
EIF2C1 ProteinQ9UL18 (Uniprot-TrEMBL)
EIF2C3 ProteinQ9H9G7 (Uniprot-TrEMBL)
EIF2C4 ProteinQ9HCK5 (Uniprot-TrEMBL)
EP300 ProteinQ09472 (Uniprot-TrEMBL)
EP300ProteinQ09472 (Uniprot-TrEMBL)
GATA1 ProteinP15976 (Uniprot-TrEMBL)
GATA1:ZFPM1ComplexR-HSA-8936469 (Reactome)
GP1BA gene ProteinENSG00000185245 (Ensembl)
GP1BA geneGeneProductENSG00000185245 (Ensembl)
GP1BAProteinP07359 (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)
H3K4me2-Nucleosome:GP1BA gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BComplexR-HSA-8936615 (Reactome)
H3K4me2-Nucleosome:ITGA2B gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BComplexR-HSA-8935737 (Reactome)
H3K4me2-Nucleosome:MIR27A gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BComplexR-HSA-8937036 (Reactome)
H3K4me2-Nucleosome:THBS1 gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BComplexR-HSA-8936977 (Reactome)
H3K4me3-Nucleosome:GP1BA gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BComplexR-HSA-8936620 (Reactome)
H3K4me3-Nucleosome:ITGA2B gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BComplexR-HSA-8936485 (Reactome)
H3K4me3-Nucleosome:MIR27A gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BComplexR-HSA-8937048 (Reactome)
H3K4me3-Nucleosome:THBS1 gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BComplexR-HSA-8937013 (Reactome)
HDAC1 ProteinQ13547 (Uniprot-TrEMBL)
HDAC1ProteinQ13547 (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)
ITGA2B gene ProteinENSG00000005961 (Ensembl)
ITGA2B geneGeneProductENSG00000005961 (Ensembl)
ITGA2B(32-1039)ProteinP08514 (Uniprot-TrEMBL)
KAT2B ProteinQ92831 (Uniprot-TrEMBL)
KAT2BProteinQ92831 (Uniprot-TrEMBL)
KMT2A ProteinQ03164 (Uniprot-TrEMBL)
KMT2B ProteinQ9UMN6 (Uniprot-TrEMBL)
KMT2C ProteinQ8NEZ4 (Uniprot-TrEMBL)
KMT2D ProteinO14686 (Uniprot-TrEMBL)
KMT2E ProteinQ8IZD2 (Uniprot-TrEMBL)
MIR27A gene ProteinENSG00000207808 (Ensembl)
MIR27A geneGeneProductENSG00000207808 (Ensembl)
MOV10 ProteinQ9HCE1 (Uniprot-TrEMBL)
MYL9 gene ProteinENSG00000101335 (Ensembl)
MYL9 geneGeneProductENSG00000101335 (Ensembl)
MYL9ProteinP24844 (Uniprot-TrEMBL)
Me2K5,Me2aR2-H3F3A ProteinP84243 (Uniprot-TrEMBL)
Me2K5,Me2aR3-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
Me2K5,Me2aR3-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
Me2K5-H3F3A ProteinP84243 (Uniprot-TrEMBL)
Me2K5-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
Me2K5-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
Me3K5-H3F3A ProteinP84243 (Uniprot-TrEMBL)
Me3K5-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
Me3K5-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
MeR206,MeR210-RUNX1 ProteinQ01196 (Uniprot-TrEMBL)
MeR206,MeR210-RUNX1:CBFB:PRMT1ComplexR-HSA-8935724 (Reactome)
NFE2 gene ProteinENSG00000123405 (Ensembl)
NFE2 geneGeneProductENSG00000123405 (Ensembl)
NFE2ProteinQ16621 (Uniprot-TrEMBL)
NR4A3 gene ProteinENSG00000119508 (Ensembl)
NR4A3 geneGeneProductENSG00000119508 (Ensembl)
NR4A3ProteinQ92570 (Uniprot-TrEMBL)
Nucleosome with H3K4me2ComplexR-HSA-1214200 (Reactome)
PF4 gene ProteinENSG00000163737 (Ensembl)
PF4 geneGeneProductENSG00000163737 (Ensembl)
PF4(32-101) ProteinP02776 (Uniprot-TrEMBL)
PF4(48-101) ProteinP02776 (Uniprot-TrEMBL)
PF4ComplexR-HSA-8938182 (Reactome)
PRKCQ gene ProteinENSG00000065675 (Ensembl)
PRKCQ geneGeneProductENSG00000065675 (Ensembl)
PRKCQProteinQ04759 (Uniprot-TrEMBL)
PRMT1 ProteinQ99873 (Uniprot-TrEMBL)
PRMT1ProteinQ99873 (Uniprot-TrEMBL)
PRMT6 ProteinQ96LA8 (Uniprot-TrEMBL)
PRMT6ProteinQ96LA8 (Uniprot-TrEMBL)
RBBP5 ProteinQ15291 (Uniprot-TrEMBL)
RUNX1 ProteinQ01196 (Uniprot-TrEMBL)
RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1ComplexR-HSA-8935716 (Reactome)
RUNX1:CBFB:MYL9 geneComplexR-HSA-8938205 (Reactome)
RUNX1:CBFB:NFE2 geneComplexR-HSA-8938329 (Reactome)
RUNX1:CBFB:NR4A3 geneComplexR-HSA-8938010 (Reactome)
RUNX1:CBFB:PF4 geneComplexR-HSA-8938178 (Reactome)
RUNX1:CBFB:PRKCQ geneComplexR-HSA-8938154 (Reactome)
RUNX1:CBFB:PRMT1ComplexR-HSA-8934741 (Reactome)
RUNX1:CBFB:SIN3A(SIN3B):PRMT6:HDAC1ComplexR-HSA-8935726 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:GP1BA gene:H3K4me2,H3R2me2a-NucleosomeComplexR-HSA-8936607 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:GP1BA gene:H3K4me2-NucleosomeComplexR-HSA-8936600 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:ITGA2B gene:H3K4me2,H3R2me2a-NucleosomeComplexR-HSA-8936586 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:ITGA2B gene:H3K4me2-NucleosomeComplexR-HSA-8935719 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:MIR27A gene:H3K4me2,H3R2me2a-NucleosomeComplexR-HSA-8937112 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:MIR27A gene:H3K4me2-NucleosomeComplexR-HSA-8937114 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:THBS1 gene:H3K4me2-NucleosomeComplexR-HSA-8936988 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:THBS1B gene:H3K4me2,H3R2me2a-NucleosomeComplexR-HSA-8937024 (Reactome)
RUNX1:CBFBComplexR-HSA-8865330 (Reactome)
Regulation of RUNX1

Expression and

Activity
PathwayR-HSA-8934593 (Reactome) At the level of transcription, expression of the RUNX1 transcription factor is regulated by two alternative promoters: a distal promoter, P1, and a proximal promoter, P2. P1 is more than 7 kb upstream of P2 (Ghozi et al. 1996). In mice, the Runx1 gene is preferentially transcribed from the proximal P2 promoter during generation of hematopoietic cells from hemogenic endothelium. In fully committed hematopoietic progenitors, the Runx1 gene is preferentially transcribed from the distal P1 promoter (Sroczynska et al. 2009, Bee et al. 2010). In human T cells, RUNX1 is preferentially transcribed from P1 throughout development, while developing natural killer cells transcribe RUNX1 predominantly from P2. Developing B cells transcribe low levels of RUNX1 from both promoters (Telfer and Rothenberg 2001).
RUNX1 mRNAs transcribed from alternative promoters differ in their 5'UTRs and splicing isoforms of RUNX1 have also been described. The function of alternative splice isoforms and alternative 5'UTRs has not been fully elucidated (Challen and Goodell 2010, Komeno et al. 2014).
During zebrafish hematopoiesis, RUNX1 expression increases in response to NOTCH signaling, but direct transcriptional regulation of RUNX1 by NOTCH has not been demonstrated (Burns et al. 2005). RUNX1 transcription also increases in response to WNT signaling. BothTCF7 and TCF4 bind the RUNX1 promoter (Wu et al. 2012, Hoverter et al. 2012), and RUNX1 transcription driven by the TCF binding element (TBE) in response to WNT3A treatment is inhibited by the dominant-negative mutant of TCF4 (Medina et al. 2016). In developing mouse ovary, Runx1 expression is positively regulated by Wnt4 signaling (Naillat et al. 2015).
Studies in mouse hematopoietic stem and progenitor cells imply that RUNX1 may be a direct transcriptional target of HOXB4 (Oshima et al. 2011).
Conserved cis-regulatory elements were recently identified in intron 5 of RUNX1. The RUNX1 breakpoints observed in acute myeloid leukemia (AML) with translocation (8;21), which result in expression of a fusion RUNX1-ETO protein, cluster in intron 5, in proximity to these not yet fully characterized cis regulatory elements (Rebolledo-Jaramillo et al. 2014).
At the level of translation, RUNX1 expression is regulated by various microRNAs which bind to the 3'UTR of RUNX1 mRNA and inhibit its translation through endonucleolytic and/or nonendonucleolytic mechanisms. MicroRNAs that target RUNX1 include miR-378 (Browne et al. 2016), miR-302b (Ge et al. 2014), miR-18a (Miao et al. 2015), miR-675 (Zhuang et al. 2014), miR-27a (Ben-Ami et al. 2009), miR-17, miR-20a, miR106 (Fontana et al. 2007) and miR-215 (Li et al. 2016).
At the posttranslational level, RUNX1 activity is regulated by postranslational modifications and binding to co-factors. SRC family kinases phosphorylate RUNX1 on multiple tyrosine residues in the negative regulatory domain, involved in autoinhibition of RUNX1. RUNX1 tyrosine phosphorylation correlates with reduced binding of RUNX1 to GATA1 and increased binding of RUNX1 to the SWI/SNF complex, leading to inhibition of RUNX1-mediated differentiation of T-cells and megakaryocytes. SHP2 (PTPN11) tyrosine phosphatase binds to RUNX1 and dephosphorylates it (Huang et al. 2012).
Formation of the complex with CBFB is necessary for the transcriptional activity of RUNX1 (Wang et al. 1996). Binding of CCND3 and probably other two cyclin D family members, CCND1 and CCND2, to RUNX1 inhibits its association with CBFB (Peterson et al. 2005), while binding to CDK6 interferes with binding of RUNX1 to DNA without affecting formation of the RUNX1:CBFB complex. Binding of RUNX1 to PML plays a role in subnuclear targeting of RUNX1 (Nguyen et al. 2005).
RUNX1 activity and protein levels vary during the cell cycle. RUNX1 protein levels increase from G1 to S and from S to G2 phases, with no increase in RUNX1 mRNA levels. CDK1-mediated phosphorylation of RUNX1 at the G2/M transition is implicated in reduction of RUNX1 transactivation potency and may promote RUNX1 protein degradation by the anaphase promoting complex (reviewed by Friedman 2009).
SETD1A ProteinO15047 (Uniprot-TrEMBL)
SETD1B ProteinQ9UPS6 (Uniprot-TrEMBL)
SIN3A ProteinQ96ST3 (Uniprot-TrEMBL)
SIN3A,(SIN3B)ComplexR-HSA-351660 (Reactome)
SIN3B ProteinO75182 (Uniprot-TrEMBL)
THBS1 ProteinP07996 (Uniprot-TrEMBL)
THBS1 gene ProteinENSG00000137801 (Ensembl)
THBS1 geneGeneProductENSG00000137801 (Ensembl)
THBS1 trimerComplexR-HSA-549142 (Reactome)
TNRC6A ProteinQ8NDV7 (Uniprot-TrEMBL)
TNRC6B ProteinQ9UPQ9 (Uniprot-TrEMBL)
TNRC6C ProteinQ9HCJ0 (Uniprot-TrEMBL)
WDR5 ProteinP61964 (Uniprot-TrEMBL)
ZFPM1 ProteinQ8IX07 (Uniprot-TrEMBL)
miR-27a

Nonendonucleolytic

RISC
ComplexR-HSA-8937100 (Reactome) The RNA-induced silencing complex contains an Argonaute (AGO) protein, whose PAZ domain binds the 3' end of the miRNA. The PIWI domain of AGO is responsible for cleavage of target RNAs, that is, RNAs complementary to the miRNA. Only AGO2 (EIF2C2) is capable of cleavage, however. AGO1 (EIF2C1), AGO3 (EIF2C3), and AGO4 (EIF2C4) repress translation of target RNAs by binding without cleavage. In vivo, cleavage by AGO2 and repression of translation by all AGOs require interaction with a TNRC6 protein (GW182 protein) and MOV10. The interaction with TNRC6 proteins is also responsible for localizing the AGO complex to Processing Bodies (P-bodies). Tethering of the C-terminal domain of a TNRC6 protein to a mRNA is sufficient to cause repression of translation.
miR-27a ProteinMI0000085 (miRBase mature sequence)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
AdoHcyArrowR-HSA-8934735 (Reactome)
AdoHcyArrowR-HSA-8936481 (Reactome)
AdoHcyArrowR-HSA-8936584 (Reactome)
AdoHcyArrowR-HSA-8936608 (Reactome)
AdoHcyArrowR-HSA-8936621 (Reactome)
AdoHcyArrowR-HSA-8937016 (Reactome)
AdoHcyArrowR-HSA-8937022 (Reactome)
AdoHcyArrowR-HSA-8937050 (Reactome)
AdoHcyArrowR-HSA-8937113 (Reactome)
AdoMetR-HSA-8934735 (Reactome)
AdoMetR-HSA-8936481 (Reactome)
AdoMetR-HSA-8936584 (Reactome)
AdoMetR-HSA-8936608 (Reactome)
AdoMetR-HSA-8936621 (Reactome)
AdoMetR-HSA-8937016 (Reactome)
AdoMetR-HSA-8937022 (Reactome)
AdoMetR-HSA-8937050 (Reactome)
AdoMetR-HSA-8937113 (Reactome)
Core MLL complexR-HSA-8935740 (Reactome)
Core MLL complexR-HSA-8936616 (Reactome)
Core MLL complexR-HSA-8936979 (Reactome)
Core MLL complexR-HSA-8937037 (Reactome)
EP300R-HSA-8935740 (Reactome)
EP300R-HSA-8936616 (Reactome)
EP300R-HSA-8936979 (Reactome)
EP300R-HSA-8937037 (Reactome)
GATA1:ZFPM1R-HSA-8935740 (Reactome)
GATA1:ZFPM1R-HSA-8936616 (Reactome)
GATA1:ZFPM1R-HSA-8936979 (Reactome)
GATA1:ZFPM1R-HSA-8937037 (Reactome)
GP1BA geneR-HSA-8936599 (Reactome)
GP1BA geneR-HSA-8936616 (Reactome)
GP1BA geneR-HSA-8936628 (Reactome)
GP1BAArrowR-HSA-8936628 (Reactome)
H3K4me2-Nucleosome:GP1BA gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BArrowR-HSA-8936616 (Reactome)
H3K4me2-Nucleosome:GP1BA gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BR-HSA-8936621 (Reactome)
H3K4me2-Nucleosome:GP1BA gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2Bmim-catalysisR-HSA-8936621 (Reactome)
H3K4me2-Nucleosome:ITGA2B gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BArrowR-HSA-8935740 (Reactome)
H3K4me2-Nucleosome:ITGA2B gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BR-HSA-8936481 (Reactome)
H3K4me2-Nucleosome:ITGA2B gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2Bmim-catalysisR-HSA-8936481 (Reactome)
H3K4me2-Nucleosome:MIR27A gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BArrowR-HSA-8937037 (Reactome)
H3K4me2-Nucleosome:MIR27A gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BR-HSA-8937050 (Reactome)
H3K4me2-Nucleosome:MIR27A gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2Bmim-catalysisR-HSA-8937050 (Reactome)
H3K4me2-Nucleosome:THBS1 gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BArrowR-HSA-8936979 (Reactome)
H3K4me2-Nucleosome:THBS1 gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BR-HSA-8937016 (Reactome)
H3K4me2-Nucleosome:THBS1 gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2Bmim-catalysisR-HSA-8937016 (Reactome)
H3K4me3-Nucleosome:GP1BA gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BArrowR-HSA-8936621 (Reactome)
H3K4me3-Nucleosome:GP1BA gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BArrowR-HSA-8936628 (Reactome)
H3K4me3-Nucleosome:ITGA2B gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BArrowR-HSA-8935731 (Reactome)
H3K4me3-Nucleosome:ITGA2B gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BArrowR-HSA-8936481 (Reactome)
H3K4me3-Nucleosome:MIR27A gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BArrowR-HSA-8937050 (Reactome)
H3K4me3-Nucleosome:MIR27A gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BArrowR-HSA-8937097 (Reactome)
H3K4me3-Nucleosome:THBS1 gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BArrowR-HSA-8936995 (Reactome)
H3K4me3-Nucleosome:THBS1 gene:RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1:GATA1:ZFPM1:Core MLL complex:EP300:KAT2BArrowR-HSA-8937016 (Reactome)
HDAC1R-HSA-8935732 (Reactome)
ITGA2B geneR-HSA-8935730 (Reactome)
ITGA2B geneR-HSA-8935731 (Reactome)
ITGA2B geneR-HSA-8935740 (Reactome)
ITGA2B(32-1039)ArrowR-HSA-8935731 (Reactome)
KAT2BR-HSA-8935740 (Reactome)
KAT2BR-HSA-8936616 (Reactome)
KAT2BR-HSA-8936979 (Reactome)
KAT2BR-HSA-8937037 (Reactome)
MIR27A geneR-HSA-8937037 (Reactome)
MIR27A geneR-HSA-8937097 (Reactome)
MIR27A geneR-HSA-8937118 (Reactome)
MYL9 geneR-HSA-8938199 (Reactome)
MYL9 geneR-HSA-8938201 (Reactome)
MYL9ArrowR-HSA-8938201 (Reactome)
MeR206,MeR210-RUNX1:CBFB:PRMT1ArrowR-HSA-8934735 (Reactome)
NFE2 geneR-HSA-8938328 (Reactome)
NFE2 geneR-HSA-8938338 (Reactome)
NFE2ArrowR-HSA-8938338 (Reactome)
NR4A3 geneR-HSA-8938022 (Reactome)
NR4A3 geneR-HSA-8938034 (Reactome)
NR4A3ArrowR-HSA-8938034 (Reactome)
Nucleosome with H3K4me2R-HSA-8935730 (Reactome)
Nucleosome with H3K4me2R-HSA-8935740 (Reactome)
Nucleosome with H3K4me2R-HSA-8936599 (Reactome)
Nucleosome with H3K4me2R-HSA-8936616 (Reactome)
Nucleosome with H3K4me2R-HSA-8936979 (Reactome)
Nucleosome with H3K4me2R-HSA-8936989 (Reactome)
Nucleosome with H3K4me2R-HSA-8937037 (Reactome)
Nucleosome with H3K4me2R-HSA-8937118 (Reactome)
PF4 geneR-HSA-8938174 (Reactome)
PF4 geneR-HSA-8938176 (Reactome)
PF4ArrowR-HSA-8938174 (Reactome)
PRKCQ geneR-HSA-8938150 (Reactome)
PRKCQ geneR-HSA-8938158 (Reactome)
PRKCQArrowR-HSA-8938158 (Reactome)
PRMT1R-HSA-8934742 (Reactome)
PRMT1TBarR-HSA-8935732 (Reactome)
PRMT6R-HSA-8935732 (Reactome)
R-HSA-8934735 (Reactome) Protein arginine methyltransferase 1 (PRMT1) methylates arginine residues R206 and R210 of RUNX1. Methylation of R206 and R210 inhibits binding of co-repressors to RUNX1, thus enhancing RUNX1 transcriptional activity (Zhao et al. 2008). In mice, arginine methylation seems to be dispensable for the function of RUNX1 in definitive hematopoiesis and steady-state platelet production, but is needed for the maintenance of the peripheral population of CD4+ T cells (Mizutani et al. 2015).
R-HSA-8934742 (Reactome) RUNX1 forms a complex with protein arginine methyltransferase 1 (PRMT1) in a RNA- and DNA-independent manner. The interaction with PRMT1 involves the C-terminus of RUNX1. Since PRMT1 colocalizes with RUNX1 at RUNX1 target promoters, RUNX1 is shown as part of the RUNX1:CBFB complex (Zhao et al. 2008).
R-HSA-8935730 (Reactome) The transcriptional co-repressor SIN3A (and possibly SIN3B) can bind to the RUNX1:CBFB complex at the promoter of the ITGA2B (CD41) gene, encoding Integrin alpha IIb. Binding of SIN3A (and probably SIN3B) to RUNX1 is inhibited by PRMT1-mediated arginine methylation of RUNX1 arginine residues R206 and R210 (Zhao et al. 2008). In addition to SIN3A, the RUNX1-containing transcriptional repressor complex at the ITGA2B promoter also includes histone arginine methyltransferase PRMT6 and histone deacetylase HDAC1 (Herglotz et al. 2013). Dimethylation of histone H3 on lysine residue K4 (K5 when taking into account the initiator methionine), known as the H3K4me2 mark, is characteristic of nucleosomes associated with megakaryocyte specific promoters, including the ITGA2B gene, prior to the onset of differentiation (Herglotz et al. 2013).
R-HSA-8935731 (Reactome) The RUNX1:CBFB complex binds the promoter of the ITGA2B (CD41) gene, encoding Integrin alpha IIb, and stimulates ITGFA2B transcription. Transcription of ITGA2B is significantly upregulated by PRMT1-dependent arginine methylation of RUNX1, which interferes with the recruitment of the SIN3A (or, possibly, SIN3B) co-repressor (Zhao et al. 2008). The transcription activator complex at the ITGA2B promoter includes the RUNX1:CBFB complex, PRMT1, the GATA1:ZFPM1 complex, histone acetyltransferases p300 (EP300) and PCAF (KAT2B), and the WDR5-containing histone methyltransferase MLL complex. The MLL complex produces the activating H3K4me3 mark on nucleosomes associated with the ITGA2B gene promoter (Herglotz et al. 2013).
The transcription repressor complex at the ITGA2B promoter is formed when the SIN3A (or possibly SIN3B) co-repressor binds to the RUNX1:CBFB complex along with histone arginine methyltransferase PRMT6 and histone deacetylase HDAC1. Histone H3 arginine methylation by PRMT6 interferes with methylation of H3K4me2 to generate the activating H3K4me3 mark at the ITGA2B gene promoter, thus contributing to transcriptional repression (Herglotz et al. 2013).
ITGA2B, involved in platelet aggregation, is only expressed in maturing megakaryocytes and platelets and is a model gene for megakaryocyte specific expression (Block and Poncz 1995, Jackson 2007).
R-HSA-8935732 (Reactome) The RUNX1:CBFB complex can bind to transcriptional co-repressors SIN3A and SIN3B. The interaction with SIN3A has been studied in more detail. Binding to SIN3A leads to transcriptional repression of RUNX1 target genes, which may involve SIN3A-mediated recruitment of histone deacetylases (HDACs) to target promoters (Lutterbach et al. 2000). Arginine methylation of RUNX1 by PRMT1 inhibits association of RUNX1 with SIN3A (Zhao et al. 2008). RUNX1 transcriptional repressor complex with SIN3A also includes histone arginine methyltransferase PRMT6 and HDAC1 (Herglotz et al. 2013).
R-HSA-8935740 (Reactome) The RUNX1:CBFB complex can bind to the promoter of the ITGA2B (CD41) gene, encoding Integrin alpha-IIb, both in the absence and in the presence of PRMT1. PRMT1-mediated arginine-methylation significantly increases transcriptional activity of the RUNX1:CBFB complex at the ITGA2B promoter (Zhao et al. 2008). In addition to the RUNX1:CBFB complex, the complex of GATA1 and ZFPM1 (FOG1) (Freson et al. 2003) is also recruited to the ITGA2B promoter (Herglotz et al. 2013), likely through the interaction between GATA1 and RUNX1 (Elagib et al. 2003). The zinc finger domain of GATA1 is involved in binding to RUNX1 (Xu et al. 2006). Along with RUNX1 and GATA1, histone acetyltransferases p300 (EP300) and PCAF (KAT2B), as well as the WDR5-containing histone methyltransferase MLL complexes are also recruited to the ITGA2B promoter (Herglotz et al. 2013). Dimethylation of histone H3 on lysine residue K4 (K5 when taking into account the initiator methionine), known as the H3K4me2 mark, is characteristic of nucleosomes associated with megakaryocyte specific promoters, including the ITGA2B gene, prior to the onset of differentiation (Herglotz et al. 2013).
R-HSA-8936481 (Reactome) The WDR5-containing histone methyltransferase MLL complex, recruited to the ITGA2B promoter via RUNX1 (and possibly GATA1), methylates histone H3 on dimethylated lysine residue K4 (K5 when taking into account the initiator methionine), producing the H3K4me3 mark. The H3K4me3 mark is characteristic of nucleosomes associated with transcriptionally active promoters of megakaryocyte-specific genes (Herglotz et al. 2013).
R-HSA-8936584 (Reactome) The histone arginine methyltransferase PRMT6 asymmetrically dimethylates histone H3 on arginine residue R2 (R3 when taking into account the initiator methionine), thus creating the H3R2me2a mark on nucleosomes at the ITGA2B gene promoter. Histone H3 arginine methylation by PRMT6 interferes with methylation of H3K4me2 to generate the activating H3K4me3 mark at the ITGA2B gene promoter, thus contributing to transcriptional repression (Herglotz et al. 2013).
R-HSA-8936599 (Reactome) The transcriptional co-repressor SIN3A (and possibly SIN3B) can bind to the RUNX1:CBFB complex at the promoter of the GP1BA (CD42b) gene, encoding Platelet glycoprotein Ib alpha chain. Binding of SIN3A (and probably SIN3B) to RUNX1 is inhibited by PRMT1-mediated arginine methylation of RUNX1 arginine residues R206 and R210 (Zhao et al. 2008). In addition to SIN3A, the RUNX1-containing transcriptional repressor complex at the GP1BA promoter also includes histone arginine methyltransferase PRMT6 and histone deacetylase HDAC1 (Herglotz et al. 2013). Dimethylation of histone H3 on lysine residue K4 (K5 when taking into account the initiator methionine), known as the H3K4me2 mark, is characteristic of nucleosomes associated with megakaryocyte specific promoters, including the GP1BA gene, prior to the onset of differentiation (Herglotz et al. 2013).
R-HSA-8936608 (Reactome) The histone arginine methyltransferase PRMT6 asymmetrically dimethylates histone H3 on arginine residue R2 (R3 when taking into account the initiator methionine), thus creating the H3R2me2a mark on nucleosomes at the GP1BA gene promoter. Histone H3 arginine methylation by PRMT6 interferes with methylation of H3K4me2 to generate the activating H3K4me3 mark at the GP1BA gene promoter, thus contributing to transcriptional repression (Herglotz et al. 2013).
R-HSA-8936616 (Reactome) The RUNX1:CBFB complex can bind to the promoter of the GP1BA (CD42b) gene, encoding Platelet glycoprotein Ib alpha chain. Based on the analogy with the ITGA2B gene transcription (Zhao et al. 2008), the PRMT1-mediated arginine-methylation increases transcriptional activity of the RUNX1:CBFB complex at the GP1BA promoter (Herglotz et al. 2013). In addition to the RUNX1:CBFB complex, the complex of GATA1 and ZFPM1 (FOG1) (Freson et al. 2003) is also recruited to the GP1BA promoter (Herglotz et al. 2013), likely through the interaction between GATA1 and RUNX1 (Elagib et al. 2003). The zinc finger domain of GATA1 is involved in binding to RUNX1 (Xu et al. 2006). Along with RUNX1 and GATA1, histone acetyltransferases p300 (EP300) and PCAF (KAT2B), as well as the WDR5-containing histone methyltransferase MLL complex are also recruited to the GP1BA promoter. Dimethylation of histone H3 on lysine residue K4 (K5 when taking into account the initiator methionine), known as the H3K4me2 mark, is characteristic of nucleosomes associated with megakaryocyte specific promoters, including the GP1BA gene, prior to the onset of differentiation (Herglotz et al. 2013).
R-HSA-8936621 (Reactome) The WDR5-containing histone methyltransferase MLL complex, recruited to the GP1BA promoter via RUNX1 (and possibly GATA1), methylates histone H3 on dimethylated lysine residue K4 (K5 when taking into account the initiator methionine), producing the H3K4me3 mark. The H3K4me3 mark is characteristic of nucleosome associated with transcriptionally active promoters of megakaryocyte-specific genes (Herglotz et al. 2013).
R-HSA-8936628 (Reactome) The RUNX1:CBFB complex binds the promoter of the GP1BA (CD42b) gene, encoding Platelet glycoprotein Ib alpha chain, and stimulates GP1BA transcription. Based on analogy with the ITGA2B gene transcription, transcription of GP1BA is significantly upregulated by PRMT1-dependent arginine methylation of RUNX1, which interferes with the recruitment of the SIN3A (or, possibly, SIN3B) co-repressor (Zhao et al. 2008). The transcription activator complex at the GP1BA gene promoter includes the RUNX1:CBFB complex, PRMT1, the GATA1:ZFPM1 complex, histone acetyltransferases p300 (EP300) and PCAF (KAT2B), and the WDR5-containing histone methyltransferase MLL complex. The MLL complex produces the activating H3K4me3 mark on nucleosomes associated with the GP1BA gene promoter (Herglotz et al. 2013).
The transcription repressor complex at the GP1BA promoter is formed when the SIN3A (or possibly SIN3B) co-repressor binds to the RUNX1:CBFB complex along with histone arginine methyltransferase PRMT6 and histone deacetylase HDAC1. Histone H3 arginine methylation by PRMT6 interferes with methylation of H3K4me2 to generate the activating H3K4me3 mark at the GP1BA gene promoter, thus contributing to transcriptional repression (Herglotz et al. 2013).
Platelet glycoprotein Ib (GP-Ib) alpha chain, encoded by the GP1BA gene, is expressed at the cell surface membrane of platelets and participates in the formation of platelet plugs (Cauwenberghs et al. 2000, Jilma-Stohlawetz et al. 2003). Gp-Ib protein is first detected on the plasma membrane of maturing megakaryocytes (Debili et al. 1990).
R-HSA-8936979 (Reactome) The RUNX1:CBFB complex can bind to the promoter of the THBS1 (TSP-1) gene, encoding Thrombospondin-1. Based on the analogy with the ITGA2B gene transcription (Zhao et al. 2008), the PRMT1-mediated arginine-methylation increases transcriptional activity of the RUNX1:CBFB complex at the THBS1 promoter (Herglotz et al. 2013). In addition to the RUNX1:CBFB complex, the complex of GATA1 and ZFPM1 (FOG1) (Freson et al. 2003) is also recruited to the THBS1 promoter (Herglotz et al. 2013), likely through the interaction between GATA1 and RUNX1 (Elagib et al. 2003). The zinc finger domain of GATA1 is involved in binding to RUNX1 (Xu et al. 2006). Along with RUNX1 and GATA1, histone acetyltransferases p300 (EP300) and PCAF (KAT2B), as well as the WDR5-containing histone methyltransferase MLL complex are also recruited to the THBS1 promoter. Dimethylation of histone H3 on lysine residue K4 (K5 when taking into account the initiator methionine), known as the H3K4me2 mark, is characteristic of nucleosomes associated with megakaryocyte promoters prior to the onset of differentiation (Herglotz et al. 2013) and is assumed to be present at the THBS1 promoter.
R-HSA-8936989 (Reactome) The transcriptional co-repressor SIN3A (and possibly SIN3B) can bind to the RUNX1:CBFB complex at the promoter of the THBS1 (TSP-1) gene, encoding Thrombospondin-1. Binding of SIN3A (and probably SIN3B) to RUNX1 is inhibited by PRMT1-mediated arginine methylation of RUNX1 arginine residues R206 and R210 (Zhao et al. 2008). In addition to SIN3A, the RUNX1-containing transcriptional repressor complex at the THBS1 promoter also includes histone arginine methyltransferase PRMT6 and histone deacetylase HDAC1 (Herglotz et al. 2013). Dimethylation of histone H3 on lysine residue K4 (K5 when taking into account the initiator methionine), known as the H3K4me2 mark, is characteristic of nucleosomes associated with megakaryocyte promoters prior to the onset of differentiation (Herglotz et al. 2013), and based on epigenetic modifications that affect transactivation of the THBS1 gene (Michaud-Levesque and Richard 2009), the H3K4me2 mark is assumed to be present at the inactive THBS1 promoter.
R-HSA-8936995 (Reactome) The RUNX1:CBFB complex binds the promoter of the THBS1 (TSP-1) gene, encoding Thrombospondin-1, and stimulates THBS1 transcription. Based on the analogy with the ITGA2B gene transcription, transcription of THBS1 is significantly upregulated by PRMT1-dependent arginine methylation of RUNX1, which interferes with the recruitment of the SIN3A (or, possibly, SIN3B) co-repressor (Zhao et al. 2008). The transcription activator complex at the THBS1 gene promoter includes the RUNX1:CBFB complex, PRMT1, the GATA1:ZFPM1 complex, histone acetyltransferases p300 (EP300) and PCAF (KAT2B), and the WDR5-containing histone methyltransferase MLL complex. The MLL complex produces the activating H3K4me3 mark on nucleosomes associated with RUNX1-regulated megakaryocyte promoters (Herglotz et al. 2013). The presence of the H3K4me3 mark is characteristic of the activated THBS1 promoter (Michaud-Levesque and Richard 2009).
The transcription repressor complex at the THBS1 promoter is formed when SIN3A (or possibly SIN3B) co-repressor binds to the RUNX1:CBFB complex along with histone arginine methyltransferase PRMT6 and histone deacetylase HDAC1. Histone H3 arginine methylation by PRMT6 interferes with methylation of H3K4me2 to generate the activating H3K4me3 mark at RUNX1-regulated megakaryocyte promoters (Herglotz et al. 2013), including THBS1 promoter (Michaud-Levesque and Richard 2009).
Thrombospondin-1, encoded by the THBS1 gene, forms homotrimers which can be detected in many different cell types and are very abundant in platelet alpha granules. While THBS1 is not necessary for platelet aggregation, it contributes to stabilization of the platelet aggregate (Bonnefoy and Hoylaerts 2008).
R-HSA-8937016 (Reactome) The WDR5-containing histone methyltransferase MLL complex, recruited to the THBS1 (TSP-1) promoter via RUNX1 (and possibly GATA1), is assumed to methylate histone H3 on dimethylated lysine residue K4 (K5 when taking into account the initiator methionine), producing the H3K4me3 mark. The H3K4me3 mark is characteristic of nucleosome associated with transcriptionally active promoters of megakaryocyte-specific genes (Herglotz et al. 2013) and the appearance of the H3K4me3 mark at the THBS1 promoter coincides with THBS1 transactivation (Michaud-Levesque and Richard 2009).
R-HSA-8937022 (Reactome) The histone arginine methyltransferase PRMT6 asymmetrically dimethylates histone H3 on arginine residue R2 (R3 when taking into account the initiator methionine), thus creating the H3R2me2a mark on nucleosomes at the THBS1 gene promoter. Histone H3 arginine methylation by PRMT6 interferes with generation of the activating H3K4me3 mark at the THBS1 gene promoter, thus contributing to transcriptional repression (Michaud-Levesque and Richard 2009).
R-HSA-8937037 (Reactome) The RUNX1:CBFB complex can bind to the promoter of the MIR27A gene, encoding microRNA miR-27A (Ben-Ami et al. 2009). Based on analogy with the ITGA2B gene transcription (Zhao et al. 2008), the PRMT1-mediated arginine-methylation increases transcriptional activity of the RUNX1:CBFB complex at the MIR27A gene promoter (Herglotz et al. 2013). In addition to the RUNX1:CBFB complex, the complex of GATA1 and ZFPM1 (FOG1) (Freson et al. 2003) is also recruited to the MIR27A promoter (Herglotz et al. 2013), likely through the interaction between GATA1 and RUNX1 (Elagib et al. 2003). The zinc finger domain of GATA1 is involved in binding to RUNX1 (Xu et al. 2006). Along with RUNX1 and GATA1, histone acetyltransferases p300 (EP300) and PCAF (KAT2B), as well as the WDR5-containing histone methyltransferase MLL complex are also recruited to the MIR27A promoter. Dimethylation of histone H3 on lysine residue K4 (K5 when taking into account the initiator methionine), known as the H3K4me2 mark, is characteristic of nucleosomes associated with megakaryocyte specific promoters, including the MIR27A gene, prior to the onset of differentiation (Herglotz et al. 2013).
R-HSA-8937050 (Reactome) The WDR5-containing histone methyltransferase MLL complex, recruited to the MIR27A promoter via RUNX1 (and possibly GATA1), methylates histone H3 on dimethylated lysine residue K4 (K5 when taking into account the initiator methionine), producing the H3K4me3 mark. The H3K4me3 mark is characteristic of nucleosome associated with transcriptionally active promoters of megakaryocyte-specific genes (Herglotz et al. 2013).
R-HSA-8937097 (Reactome) The RUNX1:CBFB complex binds the promoter of the MIR27A gene, encoding microRNA miR-27a, and stimulates MIR27A transcription. Based on the analogy with the ITGA2B gene transcription, transcription of MIR27A is significantly upregulated by PRMT1-dependent arginine methylation of RUNX1, which interferes with the recruitment of the SIN3A (or, possibly, SIN3B) co-repressor (Zhao et al. 2008). The transcription activator complex at the MIR27A gene promoter includes the RUNX1:CBFB complex, PRMT1, the GATA1:ZFPM1 complex, histone acetyltransferases p300 (EP300) and PCAF (KAT2B), and the WDR5-containing histone methyltransferase MLL complex. The MLL complex produces the activating H3K4me3 mark on nucleosomes associated with the MIR27A gene promoter (Herglotz et al. 2013).
The transcription repressor complex at the MIR27A promoter is formed when SIN3A (or possibly SIN3B) co-repressor binds to the RUNX1:CBFB complex along with histone arginine methyltransferase PRMT6 and histone deacetylase HDAC1. Histone H3 arginine methylation by PRMT6 interferes with methylation of H3K4me2 to generate the activating H3K4me3 mark at the MIR27A gene promoter, thus contributing to transcriptional repression (Herglotz et al. 2013).
MicroRNA miR-27a binds the 3'UTR of RUNX1 mRNA and inhibits RUNX1 mRNA translation without affecting RUNX1 mRNA stability. RUNX1 and MIR27A thus constitute a negative feedback loop that regulates megakaryocytic differentiation and may be involved in erythroid/megakaryocytic lineage determination (Ben-Ami et al. 2009).
R-HSA-8937113 (Reactome) The histone arginine methyltransferase PRMT6 asymmetrically dimethylates histone H3 on arginine residue R2 (R3 when taking into account the initiator methionine), thus creating the H3R2me2a mark on nucleosomes at the MIR27A gene promoter. Histone H3 arginine methylation by PRMT6 interferes with generation of the activating H3K4me3 mark at the MIR27A gene promoter, thus contributing to transcriptional repression (Herglotz et al. 2013).
R-HSA-8937118 (Reactome) The transcriptional co-repressor SIN3A (and possibly SIN3B) can bind to the RUNX1:CBFB complex at the promoter of the MIR27A gene, encoding microRNA miR-27a (Ben-Ami et al. 2009, Herglotz et al. 2013). Binding of SIN3A (and probably SIN3B) to RUNX1 is inhibited by PRMT1-mediated arginine methylation of RUNX1 arginine residues R206 and R210 (Zhao et al. 2008). In addition to SIN3A, the RUNX1-containing transcriptional repressor complex at the MIR27A promoter also includes histone arginine methyltransferase PRMT6 and histone deacetylase HDAC1 (Herglotz et al. 2013). Dimethylation of histone H3 on lysine residue K4 (K5 when taking into account the initiator methionine), known as the H3K4me2 mark, is characteristic of nucleosomes associated with megakaryocyte specific promoters, including the MIR27A gene, prior to the onset of differentiation (Herglotz et al. 2013).
R-HSA-8938022 (Reactome) The RUNX1:CBFB complex bind the RUNX1 site in the promoter of the NR4A3 gene (Bluteau et al. 2011).
R-HSA-8938034 (Reactome) Binding of the RUNX1:CBFB complex to the NR4A3 gene promoter stimulates NR4A3 gene transcription, leading to reduction in the clonogenic potential of hematopoietic progenitors. RUNX1 mutants associated with familial platelet disorders (FPD) and acute myeloid leukemia (AML) are unable to transactivate the NR4A3 gene (Bluteau et al. 2011).
R-HSA-8938150 (Reactome) The RUNX1:CBFB complex binds the promoter of the PRKCQ gene, encoding Protein kinase C theta type (Jalagadugula et al. 2011).
R-HSA-8938158 (Reactome) Binding of the RUNX1:CBFB complex to the promoter of the PRKCQ gene, encoding Protein kinase C theta type, stimulates PRKCQ transcription. RUNX1 mutants associated with inherited thrombocytopenia are unable to transactivate the PRKCQ gene. PRKCQ is important for the functioning of megakaryocytes and platelets, but is not megakaryocyte specific (Jalagadugula et al. 2011).
R-HSA-8938174 (Reactome) Binding of the RUNX1:CBFB complex to the promoter of the PF4 gene stimulates transcription of PF4. The PF4 gene encodes Platelet factor 4, a protein stored in platelet alpha granules. Deficiency of alpha granule proteins, including PF4, is the cause of gray platelet syndrome. PF4 deficiency can be caused by RUNX1 haploinsuficiency (Aneja et al. 2011).
R-HSA-8938176 (Reactome) The RUNX1:CBFB complex binds to two RUNX1 response elements in the promoter of the PF4 gene, encoding Platelet factor 4 (Aneja et al. 2011).
R-HSA-8938199 (Reactome) The RUNX1:CBFB complex binds to four RUNX1 response elements in the promoter of the MYL9 gene, encoding Myosin regulatory light polypeptide 9, which functions as the regulatory subunit of the myosin complex (Jalagadugula et al. 2010).
R-HSA-8938201 (Reactome) Binding of the RUNX1:CBFB complex to the promoter of the MYL9 gene stimulates MYL9 transcription. All four RUNX1 response elements in the MYL9 promoter contribute to transactivation of the MYL9 gene. The MYL9 gene encodes Myosin regulatory light polypeptide, which functions as a regulatory subunit of the myosin complex. Myosin plays an important role in platelet activation and thrombopoiesis. RUNX1 haploinsuficiency is associated with decreased MYL9 expression and myosin light chain phosphorylation, which likely contributes to thrombocytopenia and platelet dysfunction (Jalagadugula et al. 2010).
R-HSA-8938328 (Reactome) The RUNX1:CBFB complex binds RUNX1 response elements in the promoter of the NFE2 gene, encoding Transcription factor NF-E2 45 kDa subunit (Wang et al. 2010).
R-HSA-8938338 (Reactome) Binding of the RUNX1:CBFB complex to the promoter of the NFE2 gene stimulates NFE2 transcription. The NFE2 gene encodes the Transcription factor NF-E2 45 kDa subunit. The NF-E2 transcription factor regulates erythroid and megakaryocytic maturation and differentiation and is overexpressed in myeloproliferative neoplasms (Wang et al. 2010).
RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1R-HSA-8935740 (Reactome)
RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1R-HSA-8936616 (Reactome)
RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1R-HSA-8936979 (Reactome)
RUNX1,MeR206,MeR210-RUNX1:CBFB:PRMT1R-HSA-8937037 (Reactome)
RUNX1:CBFB:MYL9 geneArrowR-HSA-8938199 (Reactome)
RUNX1:CBFB:MYL9 geneArrowR-HSA-8938201 (Reactome)
RUNX1:CBFB:NFE2 geneArrowR-HSA-8938328 (Reactome)
RUNX1:CBFB:NFE2 geneArrowR-HSA-8938338 (Reactome)
RUNX1:CBFB:NR4A3 geneArrowR-HSA-8938022 (Reactome)
RUNX1:CBFB:NR4A3 geneArrowR-HSA-8938034 (Reactome)
RUNX1:CBFB:PF4 geneArrowR-HSA-8938174 (Reactome)
RUNX1:CBFB:PF4 geneArrowR-HSA-8938176 (Reactome)
RUNX1:CBFB:PRKCQ geneArrowR-HSA-8938150 (Reactome)
RUNX1:CBFB:PRKCQ geneArrowR-HSA-8938158 (Reactome)
RUNX1:CBFB:PRMT1ArrowR-HSA-8934742 (Reactome)
RUNX1:CBFB:PRMT1R-HSA-8934735 (Reactome)
RUNX1:CBFB:PRMT1mim-catalysisR-HSA-8934735 (Reactome)
RUNX1:CBFB:SIN3A(SIN3B):PRMT6:HDAC1ArrowR-HSA-8935732 (Reactome)
RUNX1:CBFB:SIN3A(SIN3B):PRMT6:HDAC1R-HSA-8935730 (Reactome)
RUNX1:CBFB:SIN3A(SIN3B):PRMT6:HDAC1R-HSA-8936599 (Reactome)
RUNX1:CBFB:SIN3A(SIN3B):PRMT6:HDAC1R-HSA-8936989 (Reactome)
RUNX1:CBFB:SIN3A(SIN3B):PRMT6:HDAC1R-HSA-8937118 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:GP1BA gene:H3K4me2,H3R2me2a-NucleosomeArrowR-HSA-8936608 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:GP1BA gene:H3K4me2,H3R2me2a-NucleosomeTBarR-HSA-8936628 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:GP1BA gene:H3K4me2-NucleosomeArrowR-HSA-8936599 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:GP1BA gene:H3K4me2-NucleosomeR-HSA-8936608 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:GP1BA gene:H3K4me2-Nucleosomemim-catalysisR-HSA-8936608 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:ITGA2B gene:H3K4me2,H3R2me2a-NucleosomeArrowR-HSA-8936584 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:ITGA2B gene:H3K4me2,H3R2me2a-NucleosomeTBarR-HSA-8935731 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:ITGA2B gene:H3K4me2-NucleosomeArrowR-HSA-8935730 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:ITGA2B gene:H3K4me2-NucleosomeR-HSA-8936584 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:ITGA2B gene:H3K4me2-Nucleosomemim-catalysisR-HSA-8936584 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:MIR27A gene:H3K4me2,H3R2me2a-NucleosomeArrowR-HSA-8937113 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:MIR27A gene:H3K4me2,H3R2me2a-NucleosomeTBarR-HSA-8937097 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:MIR27A gene:H3K4me2-NucleosomeArrowR-HSA-8937118 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:MIR27A gene:H3K4me2-NucleosomeR-HSA-8937113 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:MIR27A gene:H3K4me2-Nucleosomemim-catalysisR-HSA-8937113 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:THBS1 gene:H3K4me2-NucleosomeArrowR-HSA-8936989 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:THBS1 gene:H3K4me2-NucleosomeR-HSA-8937022 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:THBS1 gene:H3K4me2-Nucleosomemim-catalysisR-HSA-8937022 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:THBS1B gene:H3K4me2,H3R2me2a-NucleosomeArrowR-HSA-8937022 (Reactome)
RUNX1:CBFB:SIN3A,(SIN3B):PRMT6:HDAC1:THBS1B gene:H3K4me2,H3R2me2a-NucleosomeTBarR-HSA-8936995 (Reactome)
RUNX1:CBFBR-HSA-8934742 (Reactome)
RUNX1:CBFBR-HSA-8935732 (Reactome)
RUNX1:CBFBR-HSA-8938022 (Reactome)
RUNX1:CBFBR-HSA-8938150 (Reactome)
RUNX1:CBFBR-HSA-8938176 (Reactome)
RUNX1:CBFBR-HSA-8938199 (Reactome)
RUNX1:CBFBR-HSA-8938328 (Reactome)
SIN3A,(SIN3B)R-HSA-8935732 (Reactome)
THBS1 geneR-HSA-8936979 (Reactome)
THBS1 geneR-HSA-8936989 (Reactome)
THBS1 geneR-HSA-8936995 (Reactome)
THBS1 trimerArrowR-HSA-8936995 (Reactome)
miR-27a

Nonendonucleolytic

RISC
ArrowR-HSA-8937097 (Reactome)
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