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Polycomb group multiprotein PRC2 complex; PRC2/EED-EZH2 complex; EZH2 histone methyltransferase complex (PcG)
Function:
1) distinct from PRC1 complex
2) maintenance of transcriptionally repressive state of genes throughout development
3) acts via chromatin remodeling & modification of histones, rendering chromatin heritably changed in its expressibility
4) able to mono-, di- & trimethylate Lys-27 of histone H3
5) minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 & SUZ12
6) compacts chromatin in the absence of the methyltransferase cofactor S-adenosyl-L-methionine (SAM
7) the PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B & PHF1 via the EZH2 subunit & with SIRT1 via the SUZ12 subunit
8) may associate with HDAC1
9) recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (putative)
10) genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A & retinoic acid genes
Structure:
- subunits: EED, EZH2, RBBP4, RBBP7 & SUZ12
- EZH2 is the catalytic subunit
Note:
- two variants of the PRC2 complex have been described, termed PRC3 & PRC4
- each of the three complexes may include a different complement of EED isoforms, although the precise sequences of the isoforms in each complex have not been determined
- the PRC2 & PRC4 complexes may also methylate Lys-26 of histone H1 in addition to Lys-27 of histone H3
Related
polycomb group protein (PcG)
General
histone N-methyltransferase
molecular complex
Properties
COMPARTMENT: cell nucleus
MOTIF: active site
SUBUNITS: polycomb protein EED
COMPARTMENT: cell nucleus
MOTIF: EZH2 interaction {81-441}
MOTIF: WD repeat {91-134}
WD repeat {142-185}
HIV1-MA interaction {149-303}
WD repeat {188-228}
WD repeat {234-275}
HIV1-MA interaction {301-441}
WD repeat {304-341}
WD repeat {359-399}
WD repeat {408-441}
EZH2
polycomb protein SUZ12
COMPARTMENT: cell nucleus
MOTIF: glycine-rich region {7-50}
serine-rich region {51-59}
MOTIF: serine residue (SEVERAL)
alanine-rich region {60-67}
MOTIF: alanine residue (SEVERAL)
Zn finger C2H2-type
SITE: 448-471
EFFECTOR-BOUND: Zn+2
Ser phosphorylation site {S546}
VEFS-box. {563-639}
histone-binding protein RBBP4
COMPARTMENT: cell nucleus
MOTIF: acetylation site
SITE: N-TERMINUS
EFFECTOR-BOUND: acetyl
WD repeat {122-155}
WD repeat {175-206}
WD repeat {225-256}
WD repeat {271-302}
WD repeat {315-346}
WD repeat {372-403}
histone-binding protein RBBP7
COMPARTMENT: cell nucleus
MOTIF: WD repeat {121-152}
WD repeat {174-205}
WD repeat {224-255}
WD repeat {270-301}
WD repeat {314-345}
Ser phosphorylation site {S354}
WD repeat {371-402}
Ser phosphorylation site {S413}
Thr phosphorylation site {T416}
References
- UniProt :accession Q15022
- Kuzmichev A et al
Different EZH2-containing complexes target methylation
of histone H1 or nucleosomal histone H3.
Mol Cell. 2004 Apr 23;14(2):183-93.
PMID: 15099518
- Kuzmichev A et al
Composition and histone substrates of polycomb repressive
group complexes change during cellular differentiation.
Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1859-64.
PMID: 15684044
- Martin C et al
Substrate preferences of the EZH2 histone methyltransferase
complex.
J Biol Chem. 2006 Mar 31;281(13):8365-70
PMID: 16431907
Components
histone-binding protein RBBP4; retinoblastoma-binding protein 4; RBBP-4; retinoblastoma-binding protein p48; chromatin assembly factor 1 subunit C; CAF-1 subunit C; chromatin assembly factor I p48 subunit; CAF-I 48 kD subunit; CAF-I p48; nucleosome-remodeling factor subunit RBAP48 (RBBP4, RbAp48)
histone-binding protein RBBP7; retinoblastoma-binding protein 7; RBBP-7; retinoblastoma-binding protein p46; histone acetyltransferase type B subunit 2; nucleosome-remodeling factor subunit RBAP46 (RBBP7, RBAP46, HAT2)
polycomb protein EED; hEED; WD protein associating with integrin cytoplasmic tails 1; WAIT-1 (EED)
polycomb protein SUZ12 (suppressor of zeste 12 protein homolog, joined to JAZF1 protein, chromatin precipitated E2F target 9 protein, ChET 9 protein, SUZ12, CHET9, JJAZ1, KIAA0160)