| Project/Area Number |
17390083
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Nagasaki University |
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Principal Investigator |
ITO Takashi Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (90306275)
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| Co-Investigator(Kenkyū-buntansha) |
YASUI Kyoshi Nagasaki University, Graduate School of Biomedical Sciences, Research Associate, 大学院医歯薬学総合研究科, 助手 (50372777)
NAKAGAWA Takeya Nagasaki University, Graduate School of Biomedical Sciences, Research Associate, 大学院医歯薬学総合研究科, 助手 (50363502)
沖 昌也 長崎大学, 大学院医歯薬学総合研究科, 助手 (60420626)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2006: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2005: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | histone / acetylation / phosphorylation / nucleosome / chromatin / transcription / 再構築 / エピジェネティクス / 翻訳後修飾 |
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| Research Abstract |
GenomicDNA exists as a nucleoprotein complex termed chromatin. The work is based on the hypothesis that chromatin dynamics and structure are an integral component of the analysis of DNA-dependent processes. Posttranslational histone modifications are important for the regulation of many biological phenomena. Transcriptional initiation is a key step in the control of mRNA synthesis and is essentially related to chromatin structure and histone modification. However, very little is known how histone modification affects transcriptional initiation. Here, we show that the ubiquitylation of H2A (ubH2A) correlates with silent chromatin and regulates transcriptional initiation. Levels of ubH2A vary during hepatocyte regeneration, and based on microarray expression data from regenerating liver, we have identified USP21 as a potential regulator. We have found that USP21, a ubiquitin-specific protease, catalyzes the hydrolysis of ubUSP21 in vitro. When chromatin is assembled in vitro, ubH2A, but not H2A, specifically repressed the methylation of H3K4. USP21 relieved this ubH2A-specific repression. Methylation of H3 lysine 4 appears to be the target of the ubH2A repression, as a H3 lysine 4 to arginine mutant cannot be repressed. Furthermore, in vivo electroporation of USP21 into the liver up-regulated Serpina6, a gene that is normally down-regulated during hepatocyte regeneration. In this project we clarified a novel mode of trans-histone crosstalk, in which H2A ubiquitylation controls the methylation of H3K4 resulting in regulation of transcriptional initiation.
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