A model for transmission of the H3K27me3 epigenetic mark

Klaus H Hansen; Adrian P Bracken; Diego Pasini; Nikolaj Dietrich; Simmi S Gehani; Astrid Monrad; Juri Rappsilber; Mads Lerdrup; Kristian Helin

doi:10.1038/ncb1787

A model for transmission of the H3K27me3 epigenetic mark

Klaus H Hansen, Adrian P Bracken, Diego Pasini, Nikolaj Dietrich, Simmi S Gehani, Astrid Monrad, Juri Rappsilber, Mads Lerdrup, Kristian Helin

509 Citations (Scopus)

Abstract

Organization of chromatin by epigenetic mechanisms is essential for establishing and maintaining cellular identity in developing and adult organisms. A key question that remains unresolved about this process is how epigenetic marks are transmitted to the next cell generation during cell division. Here we provide a model to explain how trimethylated Lys 27 of histone 3 (H3K27me3), which is catalysed by the EZH2-containing Polycomb Repressive Complex 2 (PRC2), is maintained in proliferating cells. We show that the PRC2 complex binds to the H3K27me3 mark and colocalizes with this mark in G1 phase and with sites of ongoing DNA replication. Efficient binding requires an intact trimeric PRC2 complex containing EZH2, EED and SUZ12, but is independent of the catalytic SET domain of EZH2. Using a heterologous reporter system, we show that transient recruitment of the PRC2 complex to chromatin, upstream of the transcriptional start site, is sufficient to maintain repression through endogenous PRC2 during subsequent cell divisions. Thus, we suggest that once the H3K27me3 is established, it recruits the PRC2 complex to maintain the mark at sites of DNA replication, leading to methylation of H3K27 on the daughter strands during incorporation of newly synthesized histones. This mechanism ensures maintenance of the H3K27me3 epigenetic mark in proliferating cells, not only during DNA replication when histones synthesized de novo are incorporated, but also outside S phase, thereby preserving chromatin structure and transcriptional programs.

Original language	English
Journal	Nature Cell Biology
Volume	10
Issue number	11
Pages (from-to)	1291-300
Number of pages	10
ISSN	1465-7392
DOIs	https://doi.org/10.1038/ncb1787
Publication status	Published - 2008

Keywords

Carrier Proteins
Catalysis
Cell Line
Cells, Cultured
Chromatin
DNA-Binding Proteins
Epigenesis, Genetic
Fibroblasts
G1 Phase
Genes, Reporter
Histones
Humans
Kidney
Luciferases
Lysine
Methylation
Models, Biological
Mutation
Nuclear Proteins
Polycomb Repressive Complex 2
Polycomb-Group Proteins
Promoter Regions, Genetic
RNA, Small Interfering
Repressor Proteins
S Phase
Transcription Factors
Transfection

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10.1038/ncb1787

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title = "A model for transmission of the H3K27me3 epigenetic mark",

abstract = "Organization of chromatin by epigenetic mechanisms is essential for establishing and maintaining cellular identity in developing and adult organisms. A key question that remains unresolved about this process is how epigenetic marks are transmitted to the next cell generation during cell division. Here we provide a model to explain how trimethylated Lys 27 of histone 3 (H3K27me3), which is catalysed by the EZH2-containing Polycomb Repressive Complex 2 (PRC2), is maintained in proliferating cells. We show that the PRC2 complex binds to the H3K27me3 mark and colocalizes with this mark in G1 phase and with sites of ongoing DNA replication. Efficient binding requires an intact trimeric PRC2 complex containing EZH2, EED and SUZ12, but is independent of the catalytic SET domain of EZH2. Using a heterologous reporter system, we show that transient recruitment of the PRC2 complex to chromatin, upstream of the transcriptional start site, is sufficient to maintain repression through endogenous PRC2 during subsequent cell divisions. Thus, we suggest that once the H3K27me3 is established, it recruits the PRC2 complex to maintain the mark at sites of DNA replication, leading to methylation of H3K27 on the daughter strands during incorporation of newly synthesized histones. This mechanism ensures maintenance of the H3K27me3 epigenetic mark in proliferating cells, not only during DNA replication when histones synthesized de novo are incorporated, but also outside S phase, thereby preserving chromatin structure and transcriptional programs.",

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author = "Hansen, {Klaus H} and Bracken, {Adrian P} and Diego Pasini and Nikolaj Dietrich and Gehani, {Simmi S} and Astrid Monrad and Juri Rappsilber and Mads Lerdrup and Kristian Helin",

year = "2008",

doi = "10.1038/ncb1787",

language = "English",

volume = "10",

pages = "1291--300",

journal = "Nature Cell Biology",

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TY - JOUR

T1 - A model for transmission of the H3K27me3 epigenetic mark

AU - Hansen, Klaus H

AU - Bracken, Adrian P

AU - Pasini, Diego

AU - Dietrich, Nikolaj

AU - Gehani, Simmi S

AU - Monrad, Astrid

AU - Rappsilber, Juri

AU - Lerdrup, Mads

AU - Helin, Kristian

PY - 2008

Y1 - 2008

N2 - Organization of chromatin by epigenetic mechanisms is essential for establishing and maintaining cellular identity in developing and adult organisms. A key question that remains unresolved about this process is how epigenetic marks are transmitted to the next cell generation during cell division. Here we provide a model to explain how trimethylated Lys 27 of histone 3 (H3K27me3), which is catalysed by the EZH2-containing Polycomb Repressive Complex 2 (PRC2), is maintained in proliferating cells. We show that the PRC2 complex binds to the H3K27me3 mark and colocalizes with this mark in G1 phase and with sites of ongoing DNA replication. Efficient binding requires an intact trimeric PRC2 complex containing EZH2, EED and SUZ12, but is independent of the catalytic SET domain of EZH2. Using a heterologous reporter system, we show that transient recruitment of the PRC2 complex to chromatin, upstream of the transcriptional start site, is sufficient to maintain repression through endogenous PRC2 during subsequent cell divisions. Thus, we suggest that once the H3K27me3 is established, it recruits the PRC2 complex to maintain the mark at sites of DNA replication, leading to methylation of H3K27 on the daughter strands during incorporation of newly synthesized histones. This mechanism ensures maintenance of the H3K27me3 epigenetic mark in proliferating cells, not only during DNA replication when histones synthesized de novo are incorporated, but also outside S phase, thereby preserving chromatin structure and transcriptional programs.

AB - Organization of chromatin by epigenetic mechanisms is essential for establishing and maintaining cellular identity in developing and adult organisms. A key question that remains unresolved about this process is how epigenetic marks are transmitted to the next cell generation during cell division. Here we provide a model to explain how trimethylated Lys 27 of histone 3 (H3K27me3), which is catalysed by the EZH2-containing Polycomb Repressive Complex 2 (PRC2), is maintained in proliferating cells. We show that the PRC2 complex binds to the H3K27me3 mark and colocalizes with this mark in G1 phase and with sites of ongoing DNA replication. Efficient binding requires an intact trimeric PRC2 complex containing EZH2, EED and SUZ12, but is independent of the catalytic SET domain of EZH2. Using a heterologous reporter system, we show that transient recruitment of the PRC2 complex to chromatin, upstream of the transcriptional start site, is sufficient to maintain repression through endogenous PRC2 during subsequent cell divisions. Thus, we suggest that once the H3K27me3 is established, it recruits the PRC2 complex to maintain the mark at sites of DNA replication, leading to methylation of H3K27 on the daughter strands during incorporation of newly synthesized histones. This mechanism ensures maintenance of the H3K27me3 epigenetic mark in proliferating cells, not only during DNA replication when histones synthesized de novo are incorporated, but also outside S phase, thereby preserving chromatin structure and transcriptional programs.

KW - Carrier Proteins

KW - Catalysis

KW - Cell Line

KW - Cells, Cultured

KW - Chromatin

KW - DNA-Binding Proteins

KW - Epigenesis, Genetic

KW - Fibroblasts

KW - G1 Phase

KW - Genes, Reporter

KW - Histones

KW - Humans

KW - Kidney

KW - Luciferases

KW - Lysine

KW - Methylation

KW - Models, Biological

KW - Mutation

KW - Nuclear Proteins

KW - Polycomb Repressive Complex 2

KW - Polycomb-Group Proteins

KW - Promoter Regions, Genetic

KW - RNA, Small Interfering

KW - Repressor Proteins

KW - S Phase

KW - Transcription Factors

KW - Transfection

U2 - 10.1038/ncb1787

DO - 10.1038/ncb1787

M3 - Journal article

C2 - 19043435

SN - 1465-7392

VL - 10

SP - 1291

EP - 1300

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 11

ER -

A model for transmission of the H3K27me3 epigenetic mark

Abstract

Keywords

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