Cited by 613Epigenetics and DNA MethylationGenomics and Chromatin DynamicsChromatin Remodeling and Cancer

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Molecular Mechanisms Directing PRC2 Recruitment and H3K27 Methylation

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Laugesen, Anne, Højfeldt, Jonas Westergaard, Helin, Kristian·2019·Molecular Cell

DOI 10.1016/j.molcel.2019.03.011PMC PMC6452890

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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.

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Authors: Laugesen, A., Højfeldt, J. W., & Helin, K.
Affiliations: University of Copenhagen (DK)
Corresponding author: Helin, Kristian
ORCID: Laugesen, Anne
Højfeldt, Jonas Westergaard
Helin, Kristian
Venue: Molecular Cell
Publisher: Elsevier BV
Published: 2019-04
Volume: 74
Issue: 1
Pages: 8-18
ISSN: 1097-2765 (ISSN-L)
DOI: 10.1016/j.molcel.2019.03.011
PMC: PMC6452890
OpenAlex: W2925415367
Cited by: 602
References: 105
Citations by year: 2026: 60 · 2025: 89 · 2024: 85 · 2023: 83 · 2022: 79 · 2021: 87 · 2020: 83 · 2019: 36
FWCI: 6.31
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
Locations: Molecular Cell (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Danmarks Grundforskningsfond (DNRF 82)
Novo Nordisk Fonden (NNF16OC0023234)
National Cancer Institute (P30CA008748)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: polycomb repressive complex 2, H3K27 methylation, histone methyltransferase, gene silencing, cancer therapy targets
MeSH terms: Animals, Histones, Humans, Lysine, Methylation, Protein Binding, DNA Methylation, Chromatin Assembly and Disassembly, Polycomb Repressive Complex 2

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Molecular Mechanisms Directing PRC2 Recruitment and H3K27 Methylation

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