Study for the molecular mechanism in an oocyte aging
| Project/Area Number |
26293364
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | National Center for Child Health and Development |
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Principal Investigator |
Akutsu Hidenori 国立研究開発法人国立成育医療研究センター, その他部局等, その他 (50347225)
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| Co-Investigator(Kenkyū-buntansha) |
菅沼 亮太 福島県立医科大学, 医学部, 講師 (30528211)
浜谷 敏生 慶應義塾大学, 医学部, 講師 (60265882)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
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| Keywords | 生殖医学 / 受精卵 / 不育症 / 女性医学 / 卵子 / X染色体 / 卵子加齢 / 老化 / 成熟 / β-Catenin |
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| Outline of Final Research Achievements |
An oocyte aging is strongly related with impairing totipotency of zygote and X-chromosome inactivation of female embryos is partially key molecule feature on acquiring totipotency. We aimed to explore molecular mechanism on X-chromosome inactivation process in preimplantation development using mice model. An our first accomplishment showed that histone 3 lysine 9 tri-methylation (H3K9me3) was involved in Xm (maternal X-chromosome)-Xist derepression from early preimplantation phases. We also found that the chromatin state at the Xist genomic locus became markedly condensed as oocyte growth proceeded. Xm-Xist was derepressed by chromatin alterations, the derepression was stably maintained and rescued paternal Xist mutational lethality, indicating that loss of Xm-Xist imprinting was irreversible. We propose that chromatin condensation and fine-tuning of Rnf12 dosage are crucial for Xist imprint maintenance by silencing Xm-Xist (Fukda, et al. Plos genetics 2016).
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Maintenance of Xist imprinting depends on chromatin condensation state and Rnf12 dosage in mice.2016
Author(s)
Fukuda, A., Mitani, A., Miyashita, T., Sado, T., Umezawa, A., and *Akutsu, H.
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Journal Title
PloS Genet.
Volume: 12(10)
Issue: 10
Pages: e1006375-e1006375
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Xenogeneic-free defined conditions for derivation and expansion of human embryonic stem cells with mesenchymal stem cells.2015
Author(s)
2.Akutsu H, Machida M, Kanzaki S, Sugawara T, Ohkura T, Nakamura N, Yamazaki-Inoue M, Miura T, Vemuri MC, Rao MS, Miyado K, Umezawa A.
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Journal Title
Regenerative Therapy
Volume: 1
Pages: 18-29
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Notch inhibition allows oncogene-independent generation of iPS cells2015
Author(s)
Ichida JK, T C W J, Williams LA, Carter AC, Shi Y, Moura MT, Ziller M, Singh S, Amabile G, Bock C, Umezawa A, Rubin LL, Bradner JE, Akutsu H, Meissner A, Eggan K
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Journal Title
Nature Chemical Biology
Volume: 1
Issue: 8
Pages: 632-639
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] ヒトES細胞2014
Author(s)
阿久津英憲
Organizer
第26回日本生命倫理学会年次大会
Place of Presentation
浜松
Year and Date
2014-10-25
Related Report
Invited
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