Epigenetics of trophoblast and embryonic stem cells by a novel histone-glycosylation
| Project/Area Number |
26252052
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Integrative animal science
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| Research Institution | Waseda University (2015-2016)
The University of Tokyo (2014) |
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Principal Investigator |
Shiota Kunio 早稲田大学, 理工学術院, 上級研究員(研究院教授) (80196352)
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| Co-Investigator(Kenkyū-buntansha) |
廣澤 瑞子 東京大学, 農学生命科学研究科, 助教 (60533982)
新井 大祐 早稲田大学, 理工学術院, 次席研究員(研究院講師) (20624951)
早川 晃司 東京大学, 大学院農学生命科学研究科(農学部), 特任助教 (50636800)
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| Project Period (FY) |
2014-06-27 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥40,170,000 (Direct Cost: ¥30,900,000、Indirect Cost: ¥9,270,000)
Fiscal Year 2016: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2015: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2014: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
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| Keywords | エピジェネティクス / ヒストン修飾 / H2A-アセチルグルコサミン（GlcNAc）修飾 / ゲノム修復 / グルコース感受性 / 栄養膜幹細胞 / 胚性幹細胞 / 進化 / Nアセチルグルコサミン（GlcNAc） / ゲノムダメージ / グリコシル化 / ゲノムワイド |
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| Outline of Final Research Achievements |
We discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Serine 40 (H2AS40Gc). The H2AS40Gc site is in the L1 loop structure where two H2A molecules interact in the nucleosome. The novel O-GlcNAcylation is specific to the Serine 40 isoforms, which emerged in Marsupialia and persisted thereafter in mammals. Targets of H2AS40Gc are distributed genome-wide and are dramatically changed during the differentiation in mouse trophoblast stem cells. The level of H2AS40Gc is also responsive to glucose level and DNA damage. Intriguingly, hyper-H2AS40Gc induced by changing glucose level or the overexpression of the H2A3 Serine 40 isoform protected the genome from DNA damage in mouse embryonic stem cells. Thus the H2AS40Gc functions DNA damage repair. Based on these data, the emergence of H2A Serine 40 and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals.
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Putative Epimutagens in Maternal Peripheral and Cord Blood Samples Identified Using Human Induced Pluripotent Stem Cells.2015
Author(s)
Arai Y, Hayakawa K, Arai D, Ito R, Iwasaki Y, Saito K, Akutsu K, Takatori S, Ishii R, Hayashi R, Izumi S, Sugino N, Kondo F, Horie M, Nakazawa H, Makino T, Hirosawa M, Shiota K, Ohgane J.
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Journal Title
Biomed Res Int
Volume: 2015
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Diabetes Induces Aberrant DNA Methylation in the Proximal Tubules of the Kidney.2015
Author(s)
Marumo T, Yagi S, Kawarazaki W, Nishimoto M, Ayuzawa N, Watanabe A, Ueda K, Hirahashi J, Hishikawa K, Sakurai H, Shiota K, Fujita T.
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Journal Title
J Am Soc Nephrol.
Volume: 印刷中
Related Report
Peer Reviewed
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