Chd2 regulates chromatin for proper gene expression toward differentiation in mouse embryonic stem cells

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Chromatin reorganization is necessary for pluripotent stem cells, including embryonic stem cells (ESCs), to acquire lineage potential. However, it remains unclear how ESCs maintain their characteristic chromatin state for appropriate gene expression upon differentiation. Here, we demonstrate that chromodomain helicase DNA-binding domain 2 (Chd2) is required to maintain the differentiation potential of mouse ESCs. Chd2-depleted ESCs showed suppressed expression of developmentally regulated genes upon differentiation and subsequent differentiation defects without affecting gene expression in the undifferentiated state. Furthermore, chromatin immunoprecipitation followed by sequencing revealed alterations in the nucleosome occupancy of the histone variant H3.3 for developmentally regulated genes in Chd2-depleted ESCs, which in turn led to elevated trimethylation of the histone H3 lysine 27. These results suggest that Chd2 is essential in preventing suppressive chromatin formation for developmentally regulated genes and determines subsequent effects on developmental processes in the undifferentiated state.

Original languageEnglish
Pages (from-to)8758-8772
Number of pages15
JournalNucleic acids research
Volume45
Issue number15
DOIs
Publication statusPublished - Sep 1 2017

Fingerprint

DNA Helicases
Embryonic Stem Cells
Chromatin
Gene Expression
Histones
Genes
Pluripotent Stem Cells
Nucleosomes
Chromatin Immunoprecipitation
Lysine
Mouse Embryonic Stem Cells

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

@article{c462423f6d034efeb017fd8536c65ec7,
title = "Chd2 regulates chromatin for proper gene expression toward differentiation in mouse embryonic stem cells",
abstract = "Chromatin reorganization is necessary for pluripotent stem cells, including embryonic stem cells (ESCs), to acquire lineage potential. However, it remains unclear how ESCs maintain their characteristic chromatin state for appropriate gene expression upon differentiation. Here, we demonstrate that chromodomain helicase DNA-binding domain 2 (Chd2) is required to maintain the differentiation potential of mouse ESCs. Chd2-depleted ESCs showed suppressed expression of developmentally regulated genes upon differentiation and subsequent differentiation defects without affecting gene expression in the undifferentiated state. Furthermore, chromatin immunoprecipitation followed by sequencing revealed alterations in the nucleosome occupancy of the histone variant H3.3 for developmentally regulated genes in Chd2-depleted ESCs, which in turn led to elevated trimethylation of the histone H3 lysine 27. These results suggest that Chd2 is essential in preventing suppressive chromatin formation for developmentally regulated genes and determines subsequent effects on developmental processes in the undifferentiated state.",
author = "Yuichiro Semba and Akihito Harada and Kazumitsu Maehara and Shinya Oki and Chikara Meno and Jun Ueda and Kazuo Yamagata and Atsushi Suzuki and Mitsuho Onimaru and Jumpei Nogami and Seiji Okada and Koichi Akashi and Yasuyuki Ohkawa",
year = "2017",
month = "9",
day = "1",
doi = "10.1093/nar/gkx475",
language = "English",
volume = "45",
pages = "8758--8772",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "15",

}

TY - JOUR

T1 - Chd2 regulates chromatin for proper gene expression toward differentiation in mouse embryonic stem cells

AU - Semba, Yuichiro

AU - Harada, Akihito

AU - Maehara, Kazumitsu

AU - Oki, Shinya

AU - Meno, Chikara

AU - Ueda, Jun

AU - Yamagata, Kazuo

AU - Suzuki, Atsushi

AU - Onimaru, Mitsuho

AU - Nogami, Jumpei

AU - Okada, Seiji

AU - Akashi, Koichi

AU - Ohkawa, Yasuyuki

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Chromatin reorganization is necessary for pluripotent stem cells, including embryonic stem cells (ESCs), to acquire lineage potential. However, it remains unclear how ESCs maintain their characteristic chromatin state for appropriate gene expression upon differentiation. Here, we demonstrate that chromodomain helicase DNA-binding domain 2 (Chd2) is required to maintain the differentiation potential of mouse ESCs. Chd2-depleted ESCs showed suppressed expression of developmentally regulated genes upon differentiation and subsequent differentiation defects without affecting gene expression in the undifferentiated state. Furthermore, chromatin immunoprecipitation followed by sequencing revealed alterations in the nucleosome occupancy of the histone variant H3.3 for developmentally regulated genes in Chd2-depleted ESCs, which in turn led to elevated trimethylation of the histone H3 lysine 27. These results suggest that Chd2 is essential in preventing suppressive chromatin formation for developmentally regulated genes and determines subsequent effects on developmental processes in the undifferentiated state.

AB - Chromatin reorganization is necessary for pluripotent stem cells, including embryonic stem cells (ESCs), to acquire lineage potential. However, it remains unclear how ESCs maintain their characteristic chromatin state for appropriate gene expression upon differentiation. Here, we demonstrate that chromodomain helicase DNA-binding domain 2 (Chd2) is required to maintain the differentiation potential of mouse ESCs. Chd2-depleted ESCs showed suppressed expression of developmentally regulated genes upon differentiation and subsequent differentiation defects without affecting gene expression in the undifferentiated state. Furthermore, chromatin immunoprecipitation followed by sequencing revealed alterations in the nucleosome occupancy of the histone variant H3.3 for developmentally regulated genes in Chd2-depleted ESCs, which in turn led to elevated trimethylation of the histone H3 lysine 27. These results suggest that Chd2 is essential in preventing suppressive chromatin formation for developmentally regulated genes and determines subsequent effects on developmental processes in the undifferentiated state.

UR - http://www.scopus.com/inward/record.url?scp=85032212993&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032212993&partnerID=8YFLogxK

U2 - 10.1093/nar/gkx475

DO - 10.1093/nar/gkx475

M3 - Article

VL - 45

SP - 8758

EP - 8772

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 15

ER -