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Mol Cell. 2019 Apr 4;74(1):8-18. doi: 10.1016/j.molcel.2019.03.011.

Molecular Mechanisms Directing PRC2 Recruitment and H3K27 Methylation.

Author information

1
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark; The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
2
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark; The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark; Cell Biology Program and Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center (MSKCC), 1275 York Avenue, New York, NY 10065, USA. Electronic address: helink@mskcc.org.

Abstract

The polycomb repressive complex 2 (PRC2) is a chromatin-associated methyltransferase catalyzing mono-, di-, and trimethylation of lysine 27 on histone H3 (H3K27). This activity is required for normal organismal development and maintenance of gene expression patterns to uphold cell identity. PRC2 function is often deregulated in disease and is a promising candidate for therapeutic targeting in cancer. In this review, we discuss the molecular mechanisms proposed to take part in modulating PRC2 recruitment and shaping H3K27 methylation patterns across the genome. This includes consideration of factors influencing PRC2 residence time on chromatin and PRC2 catalytic activity with a focus on the mechanisms giving rise to regional preferences and differential deposition of H3K27 methylation. We further discuss existing evidence for functional diversity between distinct subsets of PRC2 complexes with the aim of extracting key concepts and highlighting major open questions toward a more complete understanding of PRC2 function.

KEYWORDS:

EZH2; H3K27; PRC2; cancer; chromatin; epigenetics; gene expression; histone methylation; polycomb; transcription

PMID:
30951652
PMCID:
PMC6452890
[Available on 2020-04-04]
DOI:
10.1016/j.molcel.2019.03.011
[Indexed for MEDLINE]

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