2022 Fiscal Year Final Research Report
Role of Polycomb in tethering ncRNAs to chromatin.
| Project/Area Number |
21K19241
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Masui Osamu 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 (30579305)
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| Co-Investigator(Kenkyū-buntansha) |
加藤 雅紀 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, 上級研究員 (10625437)
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| Project Period (FY) |
2021-07-09 – 2023-03-31
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| Keywords | Xist RNA / エピジェネティクス / 遺伝子転写制御 / Non-coding RNA / RADICL-seq / Live-cell imaging |
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| Outline of Final Research Achievements |
In this study, we first performed RADICL-seq analysis, which can identify RNA-DNA interactions in a genome-wide manner, and revealed that 50% of Xist RNA changed its binding from X chromosome to autosomes upon PRC1 deletion. This result is consistent with our previous results based on RNA FISH experiments, in which ~50% of cells showed a dispersed distribution of Xist RNA in the nucleus upon PRC1 deletion. In RADICL-seq results, we also identified several other non-coding RNA candidates that had similar behavior to Xist, i.e. losing their chromatin binding upon PRC1 deletion.
By using live-cell imaging analysis of Xist RNA with 1 minute interval, we found that Xist RNA does not make any major movement in PRC1-deleted cells in this time-window, suggesting that Xist RNA has intrinsic ability to bind to chromatin and/or nuclear matrix and does not freely move around in the nucleus even in the absence of PRC1-dependent tethering to the inactive X chromosome.
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| Free Research Field |
分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
Xist RNA などのnon-coding RNAは、標的遺伝子の転写を調節して生物個体の恒常性の維持に関わり、その破綻は疾患の原因となることが知られている。従ってnon-coding RNA の作用するメカニズムを解明することは、遺伝子転写調節機構を明らかにするだけでなく、疾患の予防や治療方法の分子基盤をもたらすと期待できる。本研究では転写抑制に関わるポリコーム複合体PRC1がXist RNAなどのnon-coding RNAをクロマチンに繋留することを明らかにした。今後さらに解析を進めて、その詳細な分子メカニズムの解明を行うことを目指す。
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