Epigenome dynamics in regulation of germ cell fate via histone modification crosstalk
| Project/Area Number |
17KK0185
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2018 – 2021
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
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| Keywords | ヒストン修飾 / DNAメチル化 / クロストーク / 生殖系列遺伝子 / 胚発生 / マウス / 生殖細胞 / エピジェネティクス / 始原生殖細胞 / エピブラスト / 多能性細胞 / エピゲノム |
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| Outline of Final Research Achievements |
Silencing of a subset of germline genes is dependent upon DNA methylation post-implantation. However, these genes are generally hypomethylated in the blastocyst, implicating alternative repressive pathways before implantation. Here, we show that in pre-implantation embryos, hypomethylated promoters of germline genes bound by PRC1.6 are enriched for RING1B-dependent H2AK119ub1 and H3K9me3. Accordingly, repression of these genes shows a greater dependence on PRC1.6 than DNA methylation. In contrast, germline genes are hypermethylated after implantation and their silencing is dependent upon SETDB1, PRC1.6/RING1B and DNA methylation, with H3K9me3. Thus, germline genes are initially repressed by PRC1.6, with DNA methylation subsequently engaged in post-implantation embryos.
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| Academic Significance and Societal Importance of the Research Achievements |
生殖系列遺伝子の発生過程における早熟な発現は不妊の原因となることが示され、また、同遺伝子の体細胞系譜における異所的な発現は腫瘍形成のリスクとの関連が強く示唆されている。本研究の成果は、将来的に不妊や腫瘍形成の原因究明に役立ち、同時にPRC1.6複合体を標的とした予防手段・治療法確立の足がかりとなることが期待できる。
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Report
(5 results)
Research Products
(5 results)
