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JpxRNAは,CTCFを駆逐することによってXistを活性化する
Sha Sun1, Brian C Del Rosario, Attila Szanto
1Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Cell
|June 25, 2013
まとめ
X染色体不活性化 (XCI) は分子定位メカニズムによって調節されます. JpxRNAはCTCFタンパク質と結合し,Xist遺伝子から放出し,哺乳類のXCIを誘発する.
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:
- 哺乳類の用量補償は,XX個体におけるX染色体不活性化 (XCI) に基づいています.
- 非コーディングのXistRNAはXCIを誘発するが,その正確な調節は不明である.
- 既存のモデルは,詳細な分子洞察が欠け,X:A依存性 (X:A) のX対オートソーム比を示唆しています.
研究 の 目的:
- Xist RNA誘導とXCI開始を制御する分子因子を明らかにする.
- Xist転写の調節におけるRNAとタンパク質の相互作用を調査する.
- XCI規制におけるCTCFの役割の仕組みを理解するために.
主な方法:
- X-エンコードされたRNAとオートソームでエンコードされたタンパク質の間の分子タイトレーションを調査した.
- 前XCI細胞におけるXist転写抑制におけるCTCFタンパク質の役割を分析した.
- XistアレルとのCTCF結合に対するJpxRNAアップレギュレーションの効果を調べました.
主要な成果:
- X-エンコードされた分子であるJpx RNAがXCIの発症時にアップレギュレーションすることを実証しました.
- JpxRNAが,自体相因子であるCTCFタンパク質に結合し,Xistプロモーターから放出することを示した.
- 確認されたCTCFは,Jpx RNAによって定位されたRNA結合タンパク質であり,それによってXist転写を活性化します.
結論:
- キシスト誘導は,Jpx RNAとCTCFタンパク質の間の分子タイトレーションによって決定されます.
- JpxRNAは,CTCF媒介による抑制を逆転させることでXistを活性化します.
- このメカニズムは,RNAとタンパク質の相互作用による表遺伝的調節におけるロングノンコーディングRNAの役割を強調しています.
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