| Project/Area Number |
16K07358
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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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| Research Field |
Cell biology
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| Research Institution | Takasaki University of Health and Welfare |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | heterochromatin / rRNA / KDM2A / nucleoli / HP1 / H4K20me3 / histone methylation / リボソームRNA遺伝子 / 転写 / ヘテロクロマチン / クロマチン構造 / ヒストン / ヒストンメチル化修飾 / zf-CxxC / SF-KDM2A / クロマチン |
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| Outline of Final Research Achievements |
The mechanisms and biological significance of the control of chromatin states in rDNA are not clear. In this project, we found that reduction of rRNA transcription by KDM2A required heterochromatin protein 1 (HP1). Because HP１ binds heterochromatin histone marks, our results suggest that heterochromatin may be involved in the regulation of rRNA transcription by KDM2A. The KDM2A gene produces another protein, SF-KDM2A. We found that SF-KDM2A reduces a heterochromatin histone mark H4K20me3 and elevates rRNA transcription. These results suggest that the activity of KDM2A may be regulated by SF-KDM2A, because HP1 binds H4K20me3. Our results suggest that two products of the KDM2A gene cooperatively regulates the activity of rDNA chromatin, possible through control of the chromatin structures.
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| Academic Significance and Societal Importance of the Research Achievements |
rRNA転写は増殖の速い癌細胞で盛んに起こっており、rRNA転写の調節は癌抑制に応用されうる。今回rRNA転写に影響するrDNAクロマチン構造の変換に、KDM2A遺伝子産物及びHP1が関与するという結果を得た。これまでHP1発現の減少は癌の進行を促すと報告されてきたが、乳がん細胞ではHP1発現は維持されていた。以上はKDM2A遺伝子産物がrDNAクロマチン構造調節を介してrRNA転写を調節すること、およびKDM2A遺伝子活性を調節することによるがん治療の可能性を示唆する。
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