Reactome | PRC2 trimethylates histone H3 at lysine-27

PRC2 trimethylates histone H3 at lysine-27

Stable Identifier

R-HSA-212263

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

4/5

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PRC2 trimethylates histone H3 at lysine-27

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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).

The catalytic activity of both EZH1- and EZH2-containing PRC2 complexes is inhibited by EZHIP (also known as CXorf67) (Jain et al. 2019, Hubner et al. 2019).

Literature References

PubMed ID	Title	Journal	Year
15099518	Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3 Kuzmichev, A, Jenuwein, T, Tempst, P, Reinberg, D	Mol Cell	2004
22323599	Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27) McCabe, MT, Graves, AP, Ganji, G, Diaz, E, Halsey, WS, Jiang, Y, Smitheman, KN, Ott, HM, Pappalardi, MB, Allen, KE, Chen, SB, Della Pietra, A, Dul, E, Hughes, AM, Gilbert, SA, Thrall, SH, Tummino, PJ, Kruger, RG, Brandt, M, Schwartz, B, Creasy, CL	Proc. Natl. Acad. Sci. U.S.A.	2012
12351676	Role of histone H3 lysine 27 methylation in Polycomb-group silencing Cao, R, Wang, L, Wang, H, Xia, L, Erdjument-Bromage, H, Tempst, P, Jones, RS, Zhang, Y	Science	2002
23679895	Convergent evolution of chromatin modification by structurally distinct enzymes: comparative enzymology of histone H3 Lys²? methylation by human polycomb repressive complex 2 and vSET Swalm, BM, Hallenbeck, KK, Majer, CR, Jin, L, Scott, MP, Moyer, MP, Copeland, RA, Wigle, TJ	Biochem. J.	2013
31086175	PFA ependymoma-associated protein EZHIP inhibits PRC2 activity through a H3 K27M-like mechanism Jain, SU, Do, TJ, Lund, PJ, Rashoff, AQ, Diehl, KL, Cieslik, M, Bajic, A, Juretic, N, Deshmukh, S, Venneti, S, Muir, TW, Garcia, BA, Jabado, N, Lewis, PW	Nat Commun	2019
12435631	Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein Kuzmichev, A, Nishioka, K, Erdjument-Bromage, H, Tempst, P, Reinberg, D	Genes Dev	2002
30923826	EZHIP/CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma Hübner, JM, Müller, T, Papageorgiou, DN, Mauermann, M, Krijgsveld, J, Russell, RB, Ellison, DW, Pfister, SM, Pajtler, KW, Kool, M	Neuro Oncol	2019
16431907	Substrate preferences of the EZH2 histone methyltransferase complex Martin, C, Cao, R, Zhang, Y	J Biol Chem	2006
19026781	Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms Margueron, R, Li, G, Sarma, K, Blais, A, Zavadil, J, Woodcock, CL, Dynlacht, BD, Reinberg, D	Mol. Cell	2008