Controls of rDNA chromatin by two proteins encoded by the KDM2A gene

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07358
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Takasaki University of Health and Welfare
• Principal Investigator: Tsuneoka Makoto 高崎健康福祉大学, 薬学部, 教授 (50197745)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: heterochromatin / rRNA / KDM2A / nucleoli / HP1 / H4K20me3 / histone methylation

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.

Free Research Field

細胞生物学　分子生物学

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。