ATF7-Dependent Epigenetic Changes Are Required for the Intergenerational Effect of a Paternal Low-Protein Diet

Keisuke Yoshida; Toshio Maekawa; Nhung Hong Ly; Shin ichiro Fujita; Masafumi Muratani; Minami Ando; Yuki Katou; Hiromitsu Araki; Fumihito Miura; Katsuhiko Shirahige; Mariko Okada; Takashi Ito; Bruno Chatton; Shunsuke Ishii

doi:10.1016/j.molcel.2020.02.028

ATF7-Dependent Epigenetic Changes Are Required for the Intergenerational Effect of a Paternal Low-Protein Diet

Keisuke Yoshida, Toshio Maekawa, Nhung Hong Ly, Shin ichiro Fujita, Masafumi Muratani, Minami Ando, Yuki Katou, Hiromitsu Araki, Fumihito Miura, Katsuhiko Shirahige, Mariko Okada, Takashi Ito, Bruno Chatton, Shunsuke Ishii

Bioregulation

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38 Citations (Scopus)

Abstract

Paternal dietary conditions may contribute to metabolic disorders in offspring. We have analyzed the role of the stress-dependent epigenetic regulator cyclic AMP-dependent transcription factor 7 (ATF7) in paternal low-protein diet (pLPD)-induced gene expression changes in mouse liver. Atf7^+/– mutations cause an offspring phenotype similar to that caused by pLPD, and the effect of pLPD almost vanished when paternal Atf7^+/– mice were used. ATF7 binds to the promoter regions of ∼2,300 genes, including cholesterol biosynthesis-related and tRNA genes in testicular germ cells (TGCs). LPD induces ATF7 phosphorylation by p38 via reactive oxygen species (ROS) in TGCs. This leads to the release of ATF7 and a decrease in histone H3K9 dimethylation (H3K9me2) on its target genes. These epigenetic changes are maintained and induce expression of some tRNA fragments in spermatozoa. These results indicate that LPD-induced and ATF7-dependent epigenetic changes in TGCs play an important role in paternal diet-induced metabolic reprograming in offspring.

Original language	English
Pages (from-to)	445-458.e6
Journal	Molecular Cell
Volume	78
Issue number	3
DOIs	https://doi.org/10.1016/j.molcel.2020.02.028
Publication status	Published - May 7 2020

All Science Journal Classification (ASJC) codes

Molecular Biology
Cell Biology

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10.1016/j.molcel.2020.02.028

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@article{18e1b8ebfc4d4db99251948284ee831f,

title = "ATF7-Dependent Epigenetic Changes Are Required for the Intergenerational Effect of a Paternal Low-Protein Diet",

abstract = "Paternal dietary conditions may contribute to metabolic disorders in offspring. We have analyzed the role of the stress-dependent epigenetic regulator cyclic AMP-dependent transcription factor 7 (ATF7) in paternal low-protein diet (pLPD)-induced gene expression changes in mouse liver. Atf7+/– mutations cause an offspring phenotype similar to that caused by pLPD, and the effect of pLPD almost vanished when paternal Atf7+/– mice were used. ATF7 binds to the promoter regions of ∼2,300 genes, including cholesterol biosynthesis-related and tRNA genes in testicular germ cells (TGCs). LPD induces ATF7 phosphorylation by p38 via reactive oxygen species (ROS) in TGCs. This leads to the release of ATF7 and a decrease in histone H3K9 dimethylation (H3K9me2) on its target genes. These epigenetic changes are maintained and induce expression of some tRNA fragments in spermatozoa. These results indicate that LPD-induced and ATF7-dependent epigenetic changes in TGCs play an important role in paternal diet-induced metabolic reprograming in offspring.",

author = "Keisuke Yoshida and Toshio Maekawa and Ly, {Nhung Hong} and Fujita, {Shin ichiro} and Masafumi Muratani and Minami Ando and Yuki Katou and Hiromitsu Araki and Fumihito Miura and Katsuhiko Shirahige and Mariko Okada and Takashi Ito and Bruno Chatton and Shunsuke Ishii",

note = "Funding Information: This work was supported by the Japan Agency for Medical Research and Development (AMED; 18gm0510015h0006 , JP16am0101059 , JP16am0101060 , JP18am0101103 , and JP18am0101105 ), a Grant-in-Aid for Scientific Research on Innovative Areas from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT; 16H01413 ), the Platform Project for Supporting Drug Discovery and Life Science Research-Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS) from AMED ( JP18am0101103 ), and the Takeda Science Foundation . Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = may,

day = "7",

doi = "10.1016/j.molcel.2020.02.028",

language = "English",

volume = "78",

pages = "445--458.e6",

journal = "Molecular Cell",

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T1 - ATF7-Dependent Epigenetic Changes Are Required for the Intergenerational Effect of a Paternal Low-Protein Diet

AU - Yoshida, Keisuke

AU - Maekawa, Toshio

AU - Ly, Nhung Hong

AU - Fujita, Shin ichiro

AU - Muratani, Masafumi

AU - Ando, Minami

AU - Katou, Yuki

AU - Araki, Hiromitsu

AU - Miura, Fumihito

AU - Shirahige, Katsuhiko

AU - Okada, Mariko

AU - Ito, Takashi

AU - Chatton, Bruno

AU - Ishii, Shunsuke

N1 - Funding Information: This work was supported by the Japan Agency for Medical Research and Development (AMED; 18gm0510015h0006 , JP16am0101059 , JP16am0101060 , JP18am0101103 , and JP18am0101105 ), a Grant-in-Aid for Scientific Research on Innovative Areas from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT; 16H01413 ), the Platform Project for Supporting Drug Discovery and Life Science Research-Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS) from AMED ( JP18am0101103 ), and the Takeda Science Foundation . Publisher Copyright: © 2020 Elsevier Inc.

PY - 2020/5/7

Y1 - 2020/5/7

N2 - Paternal dietary conditions may contribute to metabolic disorders in offspring. We have analyzed the role of the stress-dependent epigenetic regulator cyclic AMP-dependent transcription factor 7 (ATF7) in paternal low-protein diet (pLPD)-induced gene expression changes in mouse liver. Atf7+/– mutations cause an offspring phenotype similar to that caused by pLPD, and the effect of pLPD almost vanished when paternal Atf7+/– mice were used. ATF7 binds to the promoter regions of ∼2,300 genes, including cholesterol biosynthesis-related and tRNA genes in testicular germ cells (TGCs). LPD induces ATF7 phosphorylation by p38 via reactive oxygen species (ROS) in TGCs. This leads to the release of ATF7 and a decrease in histone H3K9 dimethylation (H3K9me2) on its target genes. These epigenetic changes are maintained and induce expression of some tRNA fragments in spermatozoa. These results indicate that LPD-induced and ATF7-dependent epigenetic changes in TGCs play an important role in paternal diet-induced metabolic reprograming in offspring.

AB - Paternal dietary conditions may contribute to metabolic disorders in offspring. We have analyzed the role of the stress-dependent epigenetic regulator cyclic AMP-dependent transcription factor 7 (ATF7) in paternal low-protein diet (pLPD)-induced gene expression changes in mouse liver. Atf7+/– mutations cause an offspring phenotype similar to that caused by pLPD, and the effect of pLPD almost vanished when paternal Atf7+/– mice were used. ATF7 binds to the promoter regions of ∼2,300 genes, including cholesterol biosynthesis-related and tRNA genes in testicular germ cells (TGCs). LPD induces ATF7 phosphorylation by p38 via reactive oxygen species (ROS) in TGCs. This leads to the release of ATF7 and a decrease in histone H3K9 dimethylation (H3K9me2) on its target genes. These epigenetic changes are maintained and induce expression of some tRNA fragments in spermatozoa. These results indicate that LPD-induced and ATF7-dependent epigenetic changes in TGCs play an important role in paternal diet-induced metabolic reprograming in offspring.

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DO - 10.1016/j.molcel.2020.02.028

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AN - SCOPUS:85082816191

SN - 1097-2765

VL - 78

SP - 445-458.e6

JO - Molecular Cell

JF - Molecular Cell

IS - 3

ER -

ATF7-Dependent Epigenetic Changes Are Required for the Intergenerational Effect of a Paternal Low-Protein Diet

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