哺乳類のDNA複製の空間時間的な制御のためのcis要素の識別
Jiao Sima1, Abhijit Chakraborty2, Vishnu Dileep1
1Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
Cell
|January 1, 2019
まとめ
早期複製制御要素 (ERCE) と呼ばれる離散的なシス調節要素は,DNA複製のタイミング,ゲノム構造,および転写をオーケストラします. これらの要素は ゲノム構造と機能を結びつける上で 極めて重要です
科学分野:
- ゲノミクス
- 分子生物学
- エピジェネティクス
背景:
- 複製のタイミング (RT) はゲノム構造と関連しているが,規制性cis要素は不明である.
- トポロジカル・アソシエイトドメイン (TAD) はゲノムの重要な構造単位である.
研究 の 目的:
- 複製のタイミングとゲノム構造を調節する cis 要素を特定する.
- これらのプロセスを制御するTADの境界とTAD内部要素の役割を調査する.
主な方法:
- ネズミのESCにおけるCRISPR媒介の消去と逆転
- 複製のタイミング,A/B区分,TADアーキテクチャ,およびトランスクリプションの分析.
主要な成果:
- CTCFに関連したTAD境界は,複製のタイミングのために不要です.
- CTCF独立のTAD内接触部位 (ERCE) の削除は,ドメイン全体のRTシフト,AからBのコンパートメントの変化,弱まったTAD,および転写の損失を引き起こしました.
- ERCEはゲノム構造と機能を維持するために不可欠です
結論:
- 離散型シス規制要素 (ERCE) は,ドメイン全体の複製タイミング,コンパートメント化,TADアーキテクチャ,およびトランスクリプションを制御します.
- これらの発見は ゲノム構造と機能を結びつける 基本的な原理を明らかにしています
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