Molecular Mechanisms Directing PRC2 Recruitment and H3K27 Methylation

TY - JOUR

T1 - Molecular Mechanisms Directing PRC2 Recruitment and H3K27 Methylation

AU - Laugesen, Anne

AU - Højfeldt, Jonas Westergaard

AU - Helin, Kristian

PY - 2019

Y1 - 2019

N2 - 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. PRC2 function is crucial for the specification and maintenance of cellular identity during normal development and is often deregulated in disease. Laugesen et al. discuss the orchestration of PRC2 recruitment and deposition of H3K27 methylation by factors influencing PRC2 residence time at specific chromatin regions and modulating its catalytic activity.

AB - 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. PRC2 function is crucial for the specification and maintenance of cellular identity during normal development and is often deregulated in disease. Laugesen et al. discuss the orchestration of PRC2 recruitment and deposition of H3K27 methylation by factors influencing PRC2 residence time at specific chromatin regions and modulating its catalytic activity.

KW - cancer

KW - chromatin

KW - epigenetics

KW - EZH2

KW - gene expression

KW - H3K27

KW - histone methylation

KW - polycomb

KW - PRC2

KW - transcription

U2 - 10.1016/j.molcel.2019.03.011

DO - 10.1016/j.molcel.2019.03.011

M3 - Review

C2 - 30951652

AN - SCOPUS:85063219399

SN - 1097-2765

VL - 74

SP - 8

EP - 18

JO - Molecular Cell

JF - Molecular Cell

IS - 1

ER -