2021 Fiscal Year Final Research Report
Elucidation of regulation mechanisms of CpG islands via Ubiquitin-proteasome system
| Project/Area Number |
19K06621
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 43050:Genome biology-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Ito Shinsuke 国立研究開発法人理化学研究所, 生命医科学研究センター, 研究員 (50612115)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | ポリコーム / 遺伝子発現制御 / CpGアイランド / プロテアソーム / ユビキチン |
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| Outline of Final Research Achievements |
Variant PCGF1-PRC1 (PRC1.1) that contains PCGF1, KDM2B, SKP1, BCOR, PCGF1, RING1A/B, and RYBP has been reported to contribute to the initiation of PcG silencing by recognizing CpG islands (CGIs) by the CXXC domain of KDM2B and mediating H2AK119ub1 by the RING1B/PCGF1 dimer. Notably, SKP1 associates with the F-box of KDM2B, potentially forming an SCF (SKP1A/CULLIN/F-box) ubiquitin ligase complex. These apparent biochemical properties of PRC1.1 suggest that there may be additional modes of action involving ubiquitin-related regulatory systems such as the proteasome. Here, we thus set out to explore the possibility that PRC1.1 could utilize proteasome-dependent pathways to regulate the expression of PcG target genes. Indeed, we identified none-histone protein as substrates for poly-ubiquitination by PRC1.1, which lead to degradation of protein and subsequent activation of repressed genes. We have prepared manuscript for submission.
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| Free Research Field |
エピジェネティクス
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、ポリユビキチン化を介したポリコームノ分解という独自の概念を導入し、抑制された遺伝子がどのようにして活性化されるのかの解明に繋がる成果と考えている。本研究からPRC1.1がゲノム上のCGIをスキャンニングして、適切な場所では結合が維持され、不適切な場所では自己によるポリユビキチン化後にプロテアソームにより分解されるという適材適所の選択圧がかかっている事が示唆された。とりわけ、細胞が発生・分化のように状態を大きく変化する時、このPRC1.1のポリユビキチン化機能が重要になると考えている。
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