ID | 115733 |
Author |
Nakai, Yuji
Hirosaki University
Maeda, Ryo
Tokushima University
Akiyoshi, Mika
Kyoto University
Yamaguchi, Yutaro
Kyoto University
Kitano, Satsuki
Kyoto University
Miyachi, Hitoshi
Kyoto University
Nakato, Ryuichiro
The University of Tokyo
Ichiyanagi, Kenji
Nagoya University
Shirahige, Katsuhiko
The University of Tokyo
Kimura, Hiroshi
Tokyo Institute of Technology
Shinkai, Yoichi
RIKEN Advanced Science Institute
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Content Type |
Journal Article
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Description | Histone H3 lysine 9 (H3K9) methylation is unevenly distributed in mammalian chromosomes. However, the molecular mechanism controlling the uneven distribution and its biological significance remain to be elucidated. Here, we show that JMJD1A and JMJD1B preferentially target H3K9 demethylation of gene-dense regions of chromosomes, thereby establishing an H3K9 hypomethylation state in euchromatin. JMJD1A/JMJD1B-deficient embryos died soon after implantation accompanying epiblast cell death. Furthermore, combined loss of JMJD1A and JMJD1B caused perturbed expression of metabolic genes and rapid cell death in embryonic stem cells (ESCs). These results indicate that JMJD1A/JMJD1B-meditated H3K9 demethylation has critical roles for early embryogenesis and ESC maintenance. Finally, genetic rescue experiments clarified that H3K9 overmethylation by G9A was the cause of the cell death and perturbed gene expression of JMJD1A/JMJD1B-depleted ESCs. We summarized that JMJD1A and JMJD1B, in combination, ensure early embryogenesis and ESC viability by establishing the correct H3K9 methylated epigenome.
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Journal Title |
Stem Cell Reports
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ISSN | 22136711
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Publisher | International Society for Stem Cell Research|Cell Press
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Volume | 10
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Issue | 4
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Start Page | 1340
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End Page | 1354
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Published Date | 2018-03-08
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Rights | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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DOI (Published Version) | |
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language |
eng
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TextVersion |
Publisher
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departments |
Institute of Advanced Medical Sciences
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