CTCFは,差異化過程でホックスクラスターで離散的な機能クロマチンのドメインを確立します
Varun Narendra1, Pedro P Rocha2, Disi An3
1Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
Science (New York, N.Y.)
|February 28, 2015
まとめ
CCCTC結合因子 (CTCF) は,ホックス群の遺伝子領域を隔離し,発達中に細胞の同一性を維持します. CTCFの喪失は,これらの境界を破壊し,活性遺伝子が不適切に活性化することを可能にします.
科学分野:
- エピジェネティクス エピジェネティクス
- 発達生物学 発達生物学とは
- ゲノミクスゲノミクスとは
背景:
- ポリコンブとトリソラックスタンパク質は,ホックス群のエピジェネティックメモリを確立します.
- 細胞の位置的アイデンティティは,活性クロマチンの遺伝領域と抑制クロマチンの遺伝領域に依存しています.
研究 の 目的:
- ホックスクラスター内のクロマチンのドメインを隔離するCCCTC結合因子 (CTCF) の役割を調査する.
- 幹細胞の分化中にCTCFが細胞の位置的同一性を維持する方法を理解する.
主な方法:
- 子宮頸部運動ニューロンへの胚性幹細胞の微分化を研究した.
- Hoxクラスター内のCTCF結合部位の削除の影響を分析した.
- クロマチンのドメインの組織と遺伝子活性化を研究した.
主要な成果:
- CTCFは,ホックスクラスタを空間的に異なる領域に編成し,絶縁剤として作用します.
- CTCFの結合部位の削除により,活性クロマチンが抑制ドメインに拡大した.
- CTCFの喪失はトポロジカル境界を乱し,尾部ホックス遺伝子の不適切な活性化につながった.
結論:
- CTCFは,選択性ヘテロクロマチンをユークロマチンから分離するために不可欠です.
- CTCFによるこの絶縁は,離散的な細胞位置的アイデンティティを確立するために不可欠です.
- CTCFは,発達中のホックス遺伝子調節の表遺伝子記憶を維持しています.
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