Epigenetic barrier against the propagation of fluctuating gene expression in embryonic stem cells

Yuki Saito; Akira Kunitomi; Tomohisa Seki; Shugo Tohyama; Dai Kusumoto; Makoto Takei; Shin Kashimura; Hisayuki Hashimoto; Gakuto Yozu; Chikaaki Motoda; Masaya Shimojima; Toru Egashira; Mayumi Oda; Keiichi Fukuda; Shinsuke Yuasa

doi:10.1002/1873-3468.12791

Epigenetic barrier against the propagation of fluctuating gene expression in embryonic stem cells

Yuki Saito, Akira Kunitomi, Tomohisa Seki, Shugo Tohyama, Dai Kusumoto, Makoto Takei, Shin Kashimura, Hisayuki Hashimoto, Gakuto Yozu, Chikaaki Motoda, Masaya Shimojima, Toru Egashira, Mayumi Oda, Keiichi Fukuda, Shinsuke Yuasa

Research output: Contribution to journal › Article › peer-review

Abstract

The expression of pluripotency genes fluctuates in a population of embryonic stem (ES) cells and the fluctuations in the expression of some pluripotency genes correlate. However, no correlation in the fluctuation of Pou5f1, Zfp42, and Nanog expression was observed in ES cells. Correlation between Pou5f1 and Zfp42 fluctuations was demonstrated in ES cells containing a knockout in the NuRD component Mbd3. ES cells containing a triple knockout in the DNA methyltransferases Dnmt1, Dnmt3a, and Dnmt3b showed correlation between the fluctuation of Pou5f1, Zfp42, and Nanog gene expression. We suggest that an epigenetic barrier is key to preventing the propagation of fluctuating pluripotency gene expression in ES cells.

Original language	English
Pages (from-to)	2879-2889
Number of pages	11
Journal	FEBS Letters
Volume	591
Issue number	18
DOIs	https://doi.org/10.1002/1873-3468.12791
Publication status	Published - 2017 Sept

Keywords

embryonic stem cell
epigenome
fluctuation

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1002/1873-3468.12791

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title = "Epigenetic barrier against the propagation of fluctuating gene expression in embryonic stem cells",

abstract = "The expression of pluripotency genes fluctuates in a population of embryonic stem (ES) cells and the fluctuations in the expression of some pluripotency genes correlate. However, no correlation in the fluctuation of Pou5f1, Zfp42, and Nanog expression was observed in ES cells. Correlation between Pou5f1 and Zfp42 fluctuations was demonstrated in ES cells containing a knockout in the NuRD component Mbd3. ES cells containing a triple knockout in the DNA methyltransferases Dnmt1, Dnmt3a, and Dnmt3b showed correlation between the fluctuation of Pou5f1, Zfp42, and Nanog gene expression. We suggest that an epigenetic barrier is key to preventing the propagation of fluctuating pluripotency gene expression in ES cells.",

keywords = "embryonic stem cell, epigenome, fluctuation",

author = "Yuki Saito and Akira Kunitomi and Tomohisa Seki and Shugo Tohyama and Dai Kusumoto and Makoto Takei and Shin Kashimura and Hisayuki Hashimoto and Gakuto Yozu and Chikaaki Motoda and Masaya Shimojima and Toru Egashira and Mayumi Oda and Keiichi Fukuda and Shinsuke Yuasa",

note = "Funding Information: The authors thank Dr Takayuki Abe (Department of Preventive Medicine and Public Health, Keio University School of Medicine) for his advice on biostatistics analysis and all laboratory members for their critical comments and helpful discussions. This study was supported, in part, by research grants from Grants-in-Aid for Scientific Research (JSPS KAKENHI Grant Number: 15H01521, 16H02651, 16H050304, 16K15415), and Keio University Medical Science Fund. Publisher Copyright: {\textcopyright} 2017 Federation of European Biochemical Societies",

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doi = "10.1002/1873-3468.12791",

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AU - Saito, Yuki

AU - Kunitomi, Akira

AU - Seki, Tomohisa

AU - Tohyama, Shugo

AU - Kusumoto, Dai

AU - Takei, Makoto

AU - Kashimura, Shin

AU - Hashimoto, Hisayuki

AU - Yozu, Gakuto

AU - Motoda, Chikaaki

AU - Shimojima, Masaya

AU - Egashira, Toru

AU - Oda, Mayumi

AU - Fukuda, Keiichi

AU - Yuasa, Shinsuke

N1 - Funding Information: The authors thank Dr Takayuki Abe (Department of Preventive Medicine and Public Health, Keio University School of Medicine) for his advice on biostatistics analysis and all laboratory members for their critical comments and helpful discussions. This study was supported, in part, by research grants from Grants-in-Aid for Scientific Research (JSPS KAKENHI Grant Number: 15H01521, 16H02651, 16H050304, 16K15415), and Keio University Medical Science Fund. Publisher Copyright: © 2017 Federation of European Biochemical Societies

PY - 2017/9

Y1 - 2017/9

N2 - The expression of pluripotency genes fluctuates in a population of embryonic stem (ES) cells and the fluctuations in the expression of some pluripotency genes correlate. However, no correlation in the fluctuation of Pou5f1, Zfp42, and Nanog expression was observed in ES cells. Correlation between Pou5f1 and Zfp42 fluctuations was demonstrated in ES cells containing a knockout in the NuRD component Mbd3. ES cells containing a triple knockout in the DNA methyltransferases Dnmt1, Dnmt3a, and Dnmt3b showed correlation between the fluctuation of Pou5f1, Zfp42, and Nanog gene expression. We suggest that an epigenetic barrier is key to preventing the propagation of fluctuating pluripotency gene expression in ES cells.

AB - The expression of pluripotency genes fluctuates in a population of embryonic stem (ES) cells and the fluctuations in the expression of some pluripotency genes correlate. However, no correlation in the fluctuation of Pou5f1, Zfp42, and Nanog expression was observed in ES cells. Correlation between Pou5f1 and Zfp42 fluctuations was demonstrated in ES cells containing a knockout in the NuRD component Mbd3. ES cells containing a triple knockout in the DNA methyltransferases Dnmt1, Dnmt3a, and Dnmt3b showed correlation between the fluctuation of Pou5f1, Zfp42, and Nanog gene expression. We suggest that an epigenetic barrier is key to preventing the propagation of fluctuating pluripotency gene expression in ES cells.

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Epigenetic barrier against the propagation of fluctuating gene expression in embryonic stem cells

Abstract

Keywords

ASJC Scopus subject areas

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