Reactome | PRC2-EZH2 trimethylates nucleosomes associated with CDKN2A promoter

PRC2-EZH2 trimethylates nucleosomes associated with CDKN2A promoter

Stable Identifier

R-HSA-3240295

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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PRC2-EZH2 trimethylates nucleosomes associated with CDKN2A promoter

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The Polycomb repressor complex 2 (PRC2) trimethylates histone HIST1H3A (H3) on lysine residue 28, producing an H3K27Me3 mark along the CDKN2A locus. The H3K27Me3 subsequently serves as a docking site for the PRC1.4 complex that includes BMI1 and CBX8 or CBX7 and acts to repress p16INK4A and, probably p14ARF transcription (Bracken et al. 2007). Proteins of the RB family may be involved in the regulation of enzymatic activity or the recruitment of PRC2 to the CDKN2A locus (Kotake et al. 2007). Conflicting results exist on the regulation of p14ARF expression by Polycomb group (PcG) proteins involved in the formation of PRC2 and PRC1. While p14ARF does not seem to be regulated by PcGs in human fibroblasts, in contrast to mouse embryonic fibroblasts - MEFs (Bracken et al. 2007), experiments on human CD34+ bone marrow cells (Bracken et al. 2007) and U2OS osteosarcoma cell line (Voncken et al. 2005) implicate PcGs in the regulation of p14ARF transcription.

Literature References

PubMed ID	Title	Journal	Year
17210787	pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene Kotake, Y, Cao, R, Viatour, P, Sage, J, Zhang, Y, Xiong, Y	Genes Dev.	2007
17344414	The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells Bracken, AP, Kleine-Kohlbrecher, D, Dietrich, N, Pasini, D, Gargiulo, G, Beekman, C, Theilgaard-Mönch, K, Minucci, S, Porse, BT, Marine, JC, Hansen, KH, Helin, K	Genes Dev.	2007