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発生・分化過程における哺乳類染色体の普遍的構築原理とその意義
http://hdl.handle.net/10076/14256
http://hdl.handle.net/10076/142564df77161-fbe6-4dfc-aeed-faac5d8189aa
名前 / ファイル | ライセンス | アクション |
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50K17123.pdf (583.8 kB)
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Item type | 報告書 / Research Paper(1) | |||||
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公開日 | 2014-12-18 | |||||
タイトル | ||||||
言語 | ja | |||||
タイトル | 発生・分化過程における哺乳類染色体の普遍的構築原理とその意義 | |||||
言語 | ||||||
言語 | jpn | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | 染色体 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | ゲノム | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | DNA複製 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | 複製フォーク | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | クロマチン | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | エピジェネティクス | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | DNAメチル化 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | DNA損傷 | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_18ws | |||||
資源タイプ | research report | |||||
著者 |
奥村, 克純
× 奥村, 克純× 杉村, 和人 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 哺乳類染色体の構築におけるDNAメチル化の役割について研究した。マウスセントロメアヘテロクロマチン領域のメチル化阻害は,転写活性ヒストンH3.3の蓄積後にユークロマチン様ヒストン修飾が増加し,鎖の領域の転写活性化を誘導すること,複製タイミングがS期中期や後期から初期に移行することを見出し、DNAのメチル化がセントロメア周辺ヘテロクロマチンの適切な編成に不可欠であることを示した。また,DNA低メチル化によってDNA複製フォークの減速,停止を通してDNA損傷が起こることを発見し,その複製依存的DNA損傷誘導機構モデルを提案した。本研究によって,DNA低メチル化→DNA損傷→細胞死・細胞機能異常→DNA変異・細胞のがん化・老化という可能性を提唱する。 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | In mammals, DNA methylation is an important epigenetic mark that is associated with chromosome construction. Using a DNA methylation inhibitor, we found that reduced levels of DNA methylation were associated with the activation of transcription from centromere regions and a shift in replication timing of the pericenromeric regions from middle/late S to early S phase through depositing histone H3.3 on pericenromeric heterochromatin prior to the accumulation of the euchromatic histone modification, suggesting that DNA methylation is essential for proper organization of pericentromeric heterochromatin in differentiated mouse cells. We also found that DNA methyltransferase 1 knockdown or inhibition causes replication fork stalling and replication-associated DNA damages. We propose that replication stress in the course of passive DNA demethylation could be a source of spontaneous mutations and genomic instability during tumorigenesis and aging. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 2010年度~2012年度科学研究費補助金(基盤研究(B))研究成果報告書 | |||||
書誌情報 |
発行日 2013-03-31 |
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フォーマット | ||||||
内容記述タイプ | Other | |||||
内容記述 | application/pdf | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
その他のタイトル | ||||||
General principle and importance of organization of chromosome structures during mammalian development and cell differentiation | ||||||
出版者 | ||||||
出版者 | 三重大学 | |||||
科研費番号 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 22380188 | |||||
資源タイプ(三重大) | ||||||
Kaken / 科研費報告書 |