H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipocyte Differentiation

Yoshihiro Matsumura, Ryo Nakaki, Takeshi Inagaki, Ayano Yoshida, Yuka Kano, Hiroshi Kimura, Toshiya Tanaka, Shuichi Tsutsumi, Mitsuyoshi Nakao, Takefumi Doi, Kiyoko Fukami, Timothy Osborne, Tatsuhiko Kodama, Hiroyuki Aburatani, Juro Sakai

Research output: Contribution to journalArticle

Abstract

Bivalent H3K4me3 and H3K27me3 chromatin domains in embryonic stem cells keep active developmental regulatory genes expressed at very low levels and poised for activation. Here, we show an alternative and previously unknown bivalent modified histone signature in lineage-committed mesenchymal stem cells and preadipocytes that pairs H3K4me3 with H3K9me3 to maintain adipogenic master regulatory genes (Cebpa and Pparg) expressed at low levels yet poised for activation when differentiation is required. We show lineage-specific gene-body DNA methylation recruits H3K9 methyltransferase SETDB1, which methylates H3K9 immediately downstream of transcription start sites marked with H3K4me3 to establish the bivalent domain. At the Cebpa locus, this prevents transcription factor C/EBPβ binding, histone acetylation, and further H3K4me3 deposition and is associated with pausing of RNA polymerase II, which limits Cebpa gene expression and adipogenesis.

Original languageEnglish (US)
Pages (from-to)584-596
Number of pages13
JournalMolecular Cell
Volume60
Issue number4
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

DNA Methylation
Regulator Genes
Adipocytes
Histones
Chromatin
Developmental Genes
Adipogenesis
RNA Polymerase II
Transcription Initiation Site
Methyltransferases
Acetylation
Embryonic Stem Cells
Mesenchymal Stromal Cells
Transcription Factors
Gene Expression
Genes

Keywords

  • Adipogenesis
  • Bivalent chromatin domains
  • DNA methylation
  • Epigenome
  • Gene-body methylation
  • H3K27me3
  • H3K4me3
  • H3K9me3
  • Histone methylation
  • Lineage commitment
  • RNA polymerase II

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Matsumura, Y., Nakaki, R., Inagaki, T., Yoshida, A., Kano, Y., Kimura, H., ... Sakai, J. (2015). H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipocyte Differentiation. Molecular Cell, 60(4), 584-596. https://doi.org/10.1016/j.molcel.2015.10.025

H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipocyte Differentiation. / Matsumura, Yoshihiro; Nakaki, Ryo; Inagaki, Takeshi; Yoshida, Ayano; Kano, Yuka; Kimura, Hiroshi; Tanaka, Toshiya; Tsutsumi, Shuichi; Nakao, Mitsuyoshi; Doi, Takefumi; Fukami, Kiyoko; Osborne, Timothy; Kodama, Tatsuhiko; Aburatani, Hiroyuki; Sakai, Juro.

In: Molecular Cell, Vol. 60, No. 4, 01.01.2015, p. 584-596.

Research output: Contribution to journalArticle

Matsumura, Y, Nakaki, R, Inagaki, T, Yoshida, A, Kano, Y, Kimura, H, Tanaka, T, Tsutsumi, S, Nakao, M, Doi, T, Fukami, K, Osborne, T, Kodama, T, Aburatani, H & Sakai, J 2015, 'H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipocyte Differentiation', Molecular Cell, vol. 60, no. 4, pp. 584-596. https://doi.org/10.1016/j.molcel.2015.10.025
Matsumura, Yoshihiro ; Nakaki, Ryo ; Inagaki, Takeshi ; Yoshida, Ayano ; Kano, Yuka ; Kimura, Hiroshi ; Tanaka, Toshiya ; Tsutsumi, Shuichi ; Nakao, Mitsuyoshi ; Doi, Takefumi ; Fukami, Kiyoko ; Osborne, Timothy ; Kodama, Tatsuhiko ; Aburatani, Hiroyuki ; Sakai, Juro. / H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipocyte Differentiation. In: Molecular Cell. 2015 ; Vol. 60, No. 4. pp. 584-596.
@article{c9bd092c7ecd44e3ad9958dea9e7fce1,
title = "H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipocyte Differentiation",
abstract = "Bivalent H3K4me3 and H3K27me3 chromatin domains in embryonic stem cells keep active developmental regulatory genes expressed at very low levels and poised for activation. Here, we show an alternative and previously unknown bivalent modified histone signature in lineage-committed mesenchymal stem cells and preadipocytes that pairs H3K4me3 with H3K9me3 to maintain adipogenic master regulatory genes (Cebpa and Pparg) expressed at low levels yet poised for activation when differentiation is required. We show lineage-specific gene-body DNA methylation recruits H3K9 methyltransferase SETDB1, which methylates H3K9 immediately downstream of transcription start sites marked with H3K4me3 to establish the bivalent domain. At the Cebpa locus, this prevents transcription factor C/EBPβ binding, histone acetylation, and further H3K4me3 deposition and is associated with pausing of RNA polymerase II, which limits Cebpa gene expression and adipogenesis.",
keywords = "Adipogenesis, Bivalent chromatin domains, DNA methylation, Epigenome, Gene-body methylation, H3K27me3, H3K4me3, H3K9me3, Histone methylation, Lineage commitment, RNA polymerase II",
author = "Yoshihiro Matsumura and Ryo Nakaki and Takeshi Inagaki and Ayano Yoshida and Yuka Kano and Hiroshi Kimura and Toshiya Tanaka and Shuichi Tsutsumi and Mitsuyoshi Nakao and Takefumi Doi and Kiyoko Fukami and Timothy Osborne and Tatsuhiko Kodama and Hiroyuki Aburatani and Juro Sakai",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/j.molcel.2015.10.025",
language = "English (US)",
volume = "60",
pages = "584--596",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipocyte Differentiation

AU - Matsumura, Yoshihiro

AU - Nakaki, Ryo

AU - Inagaki, Takeshi

AU - Yoshida, Ayano

AU - Kano, Yuka

AU - Kimura, Hiroshi

AU - Tanaka, Toshiya

AU - Tsutsumi, Shuichi

AU - Nakao, Mitsuyoshi

AU - Doi, Takefumi

AU - Fukami, Kiyoko

AU - Osborne, Timothy

AU - Kodama, Tatsuhiko

AU - Aburatani, Hiroyuki

AU - Sakai, Juro

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Bivalent H3K4me3 and H3K27me3 chromatin domains in embryonic stem cells keep active developmental regulatory genes expressed at very low levels and poised for activation. Here, we show an alternative and previously unknown bivalent modified histone signature in lineage-committed mesenchymal stem cells and preadipocytes that pairs H3K4me3 with H3K9me3 to maintain adipogenic master regulatory genes (Cebpa and Pparg) expressed at low levels yet poised for activation when differentiation is required. We show lineage-specific gene-body DNA methylation recruits H3K9 methyltransferase SETDB1, which methylates H3K9 immediately downstream of transcription start sites marked with H3K4me3 to establish the bivalent domain. At the Cebpa locus, this prevents transcription factor C/EBPβ binding, histone acetylation, and further H3K4me3 deposition and is associated with pausing of RNA polymerase II, which limits Cebpa gene expression and adipogenesis.

AB - Bivalent H3K4me3 and H3K27me3 chromatin domains in embryonic stem cells keep active developmental regulatory genes expressed at very low levels and poised for activation. Here, we show an alternative and previously unknown bivalent modified histone signature in lineage-committed mesenchymal stem cells and preadipocytes that pairs H3K4me3 with H3K9me3 to maintain adipogenic master regulatory genes (Cebpa and Pparg) expressed at low levels yet poised for activation when differentiation is required. We show lineage-specific gene-body DNA methylation recruits H3K9 methyltransferase SETDB1, which methylates H3K9 immediately downstream of transcription start sites marked with H3K4me3 to establish the bivalent domain. At the Cebpa locus, this prevents transcription factor C/EBPβ binding, histone acetylation, and further H3K4me3 deposition and is associated with pausing of RNA polymerase II, which limits Cebpa gene expression and adipogenesis.

KW - Adipogenesis

KW - Bivalent chromatin domains

KW - DNA methylation

KW - Epigenome

KW - Gene-body methylation

KW - H3K27me3

KW - H3K4me3

KW - H3K9me3

KW - Histone methylation

KW - Lineage commitment

KW - RNA polymerase II

UR - http://www.scopus.com/inward/record.url?scp=84947738181&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947738181&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2015.10.025

DO - 10.1016/j.molcel.2015.10.025

M3 - Article

C2 - 26590716

AN - SCOPUS:84947738181

VL - 60

SP - 584

EP - 596

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 4

ER -