PRC2 methylates histones and DNA (Homo sapiens)

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2, 5, 10, 18, 20...16, 19, 23-251, 3, 6, 13, 15...234, 7-9, 11...nucleoplasmcytosolH2AFZ SUZ12 HIST1H2BN HIST2H3A Me3K-28-H3F3A HIST1H2BD Me3K-28-HIST2H3A H2AFZ PHF19 HIST1H2BJ HIST2H2AA3 HIST1H2BN AEBP2 HIST1H2AB EED HIST1H2BK HIST2H2AA3 DNMT3B SUZ12 RBBP4 HIST1H2BJ SUZ12 RBBP7 HIST3H2BB DNA HIST2H2AC HIST1H3A MTF2 H2BFS DNMT3A DNMT1,3A,3BHIST1H2AJ HIST1H2BJ HIST2H2BE HIST1H2BD HIST1H2BL HIST1H2BL HIST1H2BN HIST1H2AC HIST1H2BC DNMT1,3A,3B:PRC2:ChromatinHIST2H3A HIST1H2BH HIST1H2AD HIST1H2AB HIST1H2BM EED HIST1H4 EED HIST1H2AB RBBP7 H2AFZ DNA HIST1H4 HIST1H4 PHF1 HIST1H2BB HIST1H2BM JARID2 RBBP7 H2AFB1 RBBP7 H2AFX H2AFB1 HIST1H2BJ EED HIST1H2BJ PRC2:Chromatin(H3K27me3)HIST1H2BA H2BFS HIST1H2AJ MTF2 HIST1H4 HIST1H2BO HIST2H2BE Me3K-28-HIST1H3A HIST1H2BL HIST1H2BA DNMT3A HIST1H2BD HIST1H2BA DNA PHF19 HIST1H2BC HIST2H2AC HIST1H2AC HIST1H2BM EZH2 HIST1H2BH H2AFZ HIST1H2BK H3F3A PHF1 RBBP7 PHF19 HIST1H2BA HIST2H2AA3 H2BFS SUZ12 HIST1H2AC EED HIST1H2BC HIST1H2AD HIST2H2AC AdoHcyHIST1H2AB HIST1H2BB AdoMetHIST2H2AA3 JARID2 HIST1H2AJ RBBP7 EZH2 AdoHcyPRC2 Core:ChromatinMe3K-28-HIST1H3A H2AFB1 H2BFS H3F3A HIST1H2AJ H2AFX HIST1H3A HIST1H2AB H2AFB1 HIST1H2BO HIST1H2BO HIST1H2BC HIST1H2BH PHF1 HIST1H2AD DNMT3B HIST2H2AC HIST1H2BH DNMT1 HIST1H2BL SUZ12 AEBP2 H2AFX H2AFB1 HIST1H3A HIST1H2BO HIST1H2BB HIST1H2BK HIST1H2BK H2AFX H2AFX MTF2 H3F3A HIST2H3A HIST1H2BA HIST1H2BL HIST1H2BB DNA HIST1H2AC HIST1H2BM HIST3H2BB RBBP4 HIST2H2BE EZH2 HIST1H3A EZH2 HIST1H4 HIST3H2BB H2BFS DNMT3B HIST2H2AA3 HIST1H2BM HIST1H2BD HIST2H2BE HIST1H2BO DNA HIST1H2BH HIST1H2BC HIST1H2BB HIST1H2AD HIST2H2BE HIST1H2AC H2AFB1 H2BFS HIST1H2AJ RBBP4 RBBP4 H2AFZ HIST2H2AC HIST2H3A HIST2H2AA3 H2AFZ HIST1H4 HIST1H2BM DNMT1,3A,3B:PRC2:Chromatin (5-mC, H3K27me3)AEBP2 EED DNMT1 HIST1H2BK RBBP4 DNMT1 H3F3A ChromatinHIST1H2BC HIST1H2AC SUZ12 HIST1H2BB EZH2 HIST1H2BH HIST1H2BA HIST1H2BJ hemimethylated DNA HIST3H2BB HIST1H2BD HIST1H2AB AdoMetHIST3H2BB EZH2 HIST3H2BB HIST1H2AD Me3K-28-H3F3A DNMT3A HIST1H2AD HIST1H2BD H2AFX PRC2HIST1H2BN HIST2H2AC JARID2 HIST1H2BN HIST1H2AJ HIST1H2BL HIST2H2BE RBBP4 HIST1H2BK HIST1H2BN PRC2:ChromatinMe3K-28-HIST2H3A HIST1H2BO 22, 26, 27


Description

Polycomb group proteins are responsible for the heritable repression of genes during development (Lee et al. 2006, Ku et al. 2008, reviewed in Simon and Kingston 2009, Margueron and Reinberg 2011, Di Croce and Helin 2013). Two major families of Polycomb complexes exist: Polycomb Repressive Complex 1 (PRC1) and Polycomb Repressive Complex 2 (PRC2). PRC1 and PRC2 each appear to comprise sets of distinct complexes that contain common core subunits and distinct accessory subunits (reviewed in Nayak et al. 2011). PRC2, through its component EZH2 or, in some complexes, EZH1 produces the initial molecular mark of repression, the trimethylation of lysine-27 of histone H3 (H3K27me3). How PRC2 is initially recruited to a locus remains unknown, however cytosine-guanine (CpG) motifs and transcripts have been suggested. Different mechanisms may be used at different loci. The trimethylated H3K27 produced by PRC2 is bound by the Polycomb subunit of PRC1. PRC1 ubiquitinates histone H2A and maintains repression. View original pathway at:Reactome.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
114960view16:48, 25 January 2021ReactomeTeamReactome version 75
113404view11:47, 2 November 2020ReactomeTeamReactome version 74
112607view15:58, 9 October 2020ReactomeTeamReactome version 73
101523view11:39, 1 November 2018ReactomeTeamreactome version 66
101059view21:21, 31 October 2018ReactomeTeamreactome version 65
100590view19:54, 31 October 2018ReactomeTeamreactome version 64
100139view16:40, 31 October 2018ReactomeTeamreactome version 63
99689view15:09, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93795view13:36, 16 August 2017ReactomeTeamreactome version 61
93332view11:20, 9 August 2017ReactomeTeamreactome version 61
88109view09:57, 26 July 2016RyanmillerOntology Term : 'regulatory pathway' added !
86418view09:17, 11 July 2016ReactomeTeamreactome version 56
83256view10:33, 18 November 2015ReactomeTeamVersion54
81366view12:53, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AEBP2 ProteinQ6ZN18 (Uniprot-TrEMBL)
AdoHcyMetaboliteCHEBI:16680 (ChEBI)
AdoMetMetaboliteCHEBI:15414 (ChEBI)
ChromatinComplexR-HSA-3211736 (Reactome)
DNA R-NUL-29428 (Reactome)
DNMT1 ProteinP26358 (Uniprot-TrEMBL)
DNMT1,3A,3B:PRC2:Chromatin (5-mC, H3K27me3)ComplexR-HSA-3211699 (Reactome) The Polycomb Repressor Complex 2 (PRC2) is able to interact with and recruit DNMT1, DNMT3a, and DNMT3b, all of which transfer a methyl group from S-adenosylmethionine to the 5 position of the cytosine ring.EZH2 is required for DNA methylation at PRC2 targets.
DNMT1,3A,3B:PRC2:ChromatinComplexR-HSA-212288 (Reactome) The Polycomb Repressor Complex 2 (PRC2) is able to interact with and recruit DNMT1, DNMT3a, and DNMT3b, all of which transfer a methyl group from S-adenosylmethionine to the 5 position of the cytosine ring.EZH2 is required for DNA methylation at PRC2 targets.
DNMT1,3A,3BComplexR-HSA-212315 (Reactome)
DNMT3A ProteinQ9Y6K1 (Uniprot-TrEMBL)
DNMT3B ProteinQ9UBC3 (Uniprot-TrEMBL)
EED ProteinO75530 (Uniprot-TrEMBL)
EZH2 ProteinQ15910 (Uniprot-TrEMBL)
H2AFB1 ProteinP0C5Y9 (Uniprot-TrEMBL)
H2AFX ProteinP16104 (Uniprot-TrEMBL)
H2AFZ ProteinP0C0S5 (Uniprot-TrEMBL)
H2BFS ProteinP57053 (Uniprot-TrEMBL)
H3F3A ProteinP84243 (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)
HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
HIST1H4 ProteinP62805 (Uniprot-TrEMBL)
HIST2H2AA3 ProteinQ6FI13 (Uniprot-TrEMBL)
HIST2H2AC ProteinQ16777 (Uniprot-TrEMBL)
HIST2H2BE ProteinQ16778 (Uniprot-TrEMBL)
HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
HIST3H2BB ProteinQ8N257 (Uniprot-TrEMBL)
JARID2 ProteinQ92833 (Uniprot-TrEMBL)
MTF2 ProteinQ9Y483 (Uniprot-TrEMBL)
Me3K-28-H3F3A ProteinP84243 (Uniprot-TrEMBL)
Me3K-28-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
Me3K-28-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
PHF1 ProteinO43189 (Uniprot-TrEMBL)
PHF19 ProteinQ5T6S3 (Uniprot-TrEMBL)
PRC2 Core:ChromatinComplexR-HSA-5084071 (Reactome)
PRC2:Chromatin (H3K27me3)ComplexR-HSA-3211731 (Reactome)
PRC2:ChromatinComplexR-HSA-3211709 (Reactome)
PRC2ComplexR-HSA-5084084 (Reactome)
RBBP4 ProteinQ09028 (Uniprot-TrEMBL)
RBBP7 ProteinQ16576 (Uniprot-TrEMBL)
SUZ12 ProteinQ15022 (Uniprot-TrEMBL)
hemimethylated DNA R-NUL-212017 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
AdoHcyArrowR-HSA-212263 (Reactome)
AdoHcyArrowR-HSA-212269 (Reactome)
AdoMetR-HSA-212263 (Reactome)
AdoMetR-HSA-212269 (Reactome)
ChromatinR-HSA-212252 (Reactome)
DNMT1,3A,3B:PRC2:Chromatin (5-mC, H3K27me3)ArrowR-HSA-212269 (Reactome)
DNMT1,3A,3B:PRC2:ChromatinArrowR-HSA-212222 (Reactome)
DNMT1,3A,3B:PRC2:ChromatinR-HSA-212269 (Reactome)
DNMT1,3A,3B:PRC2:Chromatinmim-catalysisR-HSA-212269 (Reactome)
DNMT1,3A,3BR-HSA-212222 (Reactome)
PRC2 Core:ChromatinR-HSA-212222 (Reactome)
PRC2:Chromatin (H3K27me3)ArrowR-HSA-212263 (Reactome)
PRC2:ChromatinArrowR-HSA-212252 (Reactome)
PRC2:ChromatinR-HSA-212263 (Reactome)
PRC2:Chromatinmim-catalysisR-HSA-212263 (Reactome)
PRC2R-HSA-212252 (Reactome)
R-HSA-212222 (Reactome) In tumor cells the Polycomb Repressor Complex 2 associates with a DNA methyltransferase (DNMT) via the N-terminal region of EZH2 (Vire et al. 2006). DNMT1, DNMT3a, and DNMT3b can each bind EZH2 though only one is bound at any time. As inferred from mouse (Rush et al. 2009), EZH2 tethered to a locus is able to recruit Dnmt3a but additional factors may be required to trigger de novo DNA methylation. It is unknown if the DNMT is recruited only after PRC2 has been targeted to a locus.
R-HSA-212252 (Reactome) The core of the Polycomb Repressor Complex 2 (PRC2) contains EZH2, EED, SUV12, RpAp46, and RpAp48 (Kuzzmichev et al. 2002, Cao et al. 2002). PRC2 complexes at different sites in the genome contain the core subunits plus different accessory subunits. In Drosophila PRC2 is recruited to chromatin by specific DNA sequences. In vertebrates PRC2 appears to be recruited to chromatin through several mechanisms: some (about 20%) of noncoding RNAs tethered to the locus of origin recruit PRC2 via the RNA-binding activity of EZH2 (Zhao et al. 2008, Khalil et al. 2009), GC-rich sequence elements in DNA (Mendenhall et al. 2010) and poly(ADP-ribosyl) polymerase at sites of DNA damage (Chou et al. 2010) can also recruit polycomb components, The DNA-binding proteins JARID2, AEBP2, and YY1 recruit PRC2 (Pasini et al. 2010, Li et al. 2010, reviewed in Kim and Kim 2012). The EED subunit of PRC2 can bind existing trimethylated lysine-27 on histone H3 of PRC2 which may provide a mechanism for propagation of trimethylated lysine-27 during DNA replication (Xu et al. 2010).
R-HSA-212263 (Reactome) EZH2 , a SET domain protein, trimethylates histone H3 at lysine 27 (H3K27) and lysine 9 (H3K9) (Kuzmichev et al. 2002, Cao et al. 2002, Kuzmichev et al. 2004, Martin et al. 2006, McCabe et al. 2012, Swalm et al. 2013). EZH2 has greater activity with lysine residues that have fewer methyl groups (unmethylated:monomethylated:dimethylated=9:6:1, McCabe et al. 2012). EZH1 rather than EZH2 is present in some PRC2 complexes and can also catalyze the trimethylation of H3K27 (inferred from mouse in Shen et al. 2008), however EZH1 is also able to repress transcription without methylating histone H3 (Margueron et al. 2008).
R-HSA-212269 (Reactome) DNA methyltransferases (DNMTs) associate with EZH2 of the Polycomb Repressive Complex 2 (PRC2) and methylate the 5 position of the cytosine ring in DNA (Vire et al. 2006). The histone methyltransferase activity of EZH2 also trimethylates lysine-27 of histone H3 (H3K27me3). The promoters of the MYT, WNT1, KCNA1, and CNR1 genes are methylated on cytosine by the DNMT:PRC2 complex however not all loci that have H3K27me3 by PRC2 also have cytosine methylation (Vire et al. 2006, Brinkman et al. 2012). DNA methylation and H3K27me3 appear to be mutually exclusive in CpG islands but are compatible throughout most of the rest of the genome (Brinkman et al. 2012). In mouse, DNA methylation and H3K27me3 appear to be antagonistic at most loci: loss of DNA methylation causes increased H3K27me3 while loss of PRC2 has little effect on DNA methylation (Hagarman et al. 2013). By competing with DNMT3a,b for association with PRC2, DNMT3L may antagonize DNA methylation at sites bound by PRC2 (Neri et al. 2013).
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