高解像度のXist結合マップは,X染色体不活性化時に2段階の拡散を明らかにしています
Matthew D Simon1,2, Stefan F Pinter1,3, Rui Fang2
1Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02114.
Nature
|October 29, 2013
まとめ
XistロングノンコーディングRNA (lncRNA) は,不活性X染色体を覆い,X染色体不活性化 (XCI) を誘導する. 結核の広がりは,XCIの初期段階では2段階のメカニズムに従っているが,メンテナンス中に遺伝子に富む地域と遺伝子に乏しい地域の両方を急速にカバーする.
科学分野:
- 遺伝学 遺伝学とは
- エピジェネティクス エピジェネティクス
- 分子生物学は分子生物学である.
背景:
- X染色体不活性化 (XCI) は,哺乳類における性別間の遺伝子配分を均等にする.
- Xist長いノンコーディングRNA (lncRNA) は,XCIの開始と維持に不可欠です.
- XistがX染色体全体に広がるメカニズムは,まだ完全に理解されていません.
研究 の 目的:
- XCI中のXistの高解像度結合パターンを調査する.
- Xistの広がりの時空的動態と,表遺伝的変異体との関係を解明する.
- Xist-mediated silencingにおけるクロマチンの状態の役割を理解するために.
主な方法:
- ハイブリデーションキャプチャによるクロマチンのアクセシビリティ,次にシーケンシング (CHART-seq) を用いて,Xist結合をマッピングした.
- Xist結合は,de novo XCIの間に発達時間コースを横断して分析されました.
- シストの局所化は,ポリコンブ抑制複合体2 (PRC2) とH3K27me3マークと相関していた.
主要な成果:
- キシスト結合は2段階のメカニズムに従います:最初は遺伝子に富んだ島を標的とし,次に遺伝子に乏しい領域に広がります.
- シスト結合はPRC2とH3K27me3の密度に比例し,共移住を示唆している.
- キシストは,急性除去後数時間以内に不活性X染色体を迅速に再コーティングし,プライムクロマチンの状態を示します.
結論:
- シャストの拡散は,XCIの形成と維持の過程で,異なる段階の特定のメカニズムを示しています.
- 非活性X染色体は,Xistの急速な回復を促進するプライム化染色体状態を有する.
- これらの発見は,Xist.によるX染色体不活性化のダイナミックな調節に関する新しい洞察を提供します.
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