内遺伝的DNAメチル化は,偽転写の開始を防ぐ
Francesco Neri1,2, Stefania Rapelli3, Anna Krepelova1,3
1Human Genetics Foundation (HuGeF), via Nizza 52, 10126 Torino, Italy.
Nature
|February 23, 2017
まとめ
Dnmt3bによって誘発される遺伝子体DNAメチル化は,マウス細胞における望ましくない転写の開始を防ぐ. このエピジェネティックメカニズムは正確な遺伝子発現を保証し,癌に関連している可能性があります.
科学分野:
- エピジェネティクス
- 分子生物学
- ゲノミクス
背景:
- DNAメチル化は主に哺乳類のCpG部位で発生する.
- プロモーターメチレーションは遺伝子発現を静止しますが,遺伝子体メチレーションの役割は不明です.
- 遺伝子と体のメチル化を理解することは 遺伝子調節と病気にとって極めて重要です
研究 の 目的:
- 高度に発現する遺伝子の内遺伝的DNAメチル化の機能を調査する.
- 遺伝子体メチル化が転写を調節するメカニズムを解明する.
- エピジェネティックプロセスと癌の関係を 探求するためです
主な方法:
- マウスの胚性幹細胞における全ゲノムDNAメチル化分析
- H3K36me3のためのクロマチン免疫降水配列 (ChIP-seq)
- RNAポリメラーゼII活性と偽転写の分析
- Dnmt3bに対する酵素活性測定
主要な成果:
- Dnmt3bに依存するDNAメチル化は,偽のRNAポリメラーゼIIの侵入を防ぐ.
- このプロセスは,H3K36トリメチル化 (H3K36me3) とDnmt3bの酵素活性によって媒介されます.
- 異常なトランスクリプトは分解されるか,機能しないタンパク質に変換される.
- SetD2,H3K36me3,Dnmt3b,およびDNAメチル化を含むエピジェネティック・クロスストックは,転写の忠誠性を保証する.
結論:
- 内遺伝的DNAメチル化は,暗号化トランスクリプションの開始に対する保護として機能する.
- この表遺伝的メカニズムは,転写の精度を維持するために不可欠です.
- 内遺伝的低甲基化を含むこの経路の調節不良は,がん発症に影響を及ぼします.
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