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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
Tachibana, Makoto Tokushima University|Kyoto University KAKEN Search Researchers
Content Type
Journal Article
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.
Journal Title
Stem Cell Reports
ISSN
22136711
Publisher
International Society for Stem Cell Research|Cell Press
Volume
10
Issue
4
Start Page
1340
End Page
1354
Published Date
2018-03-08
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)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences