PERIOD1に関連したタンパク質は,哺乳類の昼間振動器の負の腕を調節する
Steven A Brown1, Juergen Ripperger, Sebastian Kadener
1Department of Molecular Biology and National Centres of Competence in Research (NCCR) Frontiers in Genetics, Sciences III, University of Geneva, 30 Quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland. steven.brown@molbio.unige.ch
まとめ
2つのタンパク質,NONOとWDR5は,PERIOD (PER) タンパク質の活性を調節することによって,昼夜リズムを調節することが判明しました. それらの減少は,細胞と果物ハエの生物学的リズムを乱します.
科学分野:
- クロノバイオロジーはクロノバイオロジーを用います.
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- シルカディアンリズムは,哺乳類のPERIOD1 (PER1) やPERIOD2 (PER2) のようなクロックタンパク質を含む負の転写フィードバックループによって生成されます.
- これらのクロックタンパク質の調節を理解することは,昼夜リズムを支えるメカニズムの解読に不可欠です.
研究 の 目的:
- PER1とPER2の活性を調節する新しい要因を特定し,特徴づけること.
- シルカディアンリズムの調節におけるNONOとWDR5の役割を調査する.
主な方法:
- NONOとWDR5.5の発現を減らすためにRNA干渉 (RNAi) が使用されました.
- シルカディアンリズムは,哺乳類の細胞と,NONO発現が変化した果物ハエで評価されました.
- 時計遺伝子のプロモーターにおけるヒストンのメチル化が,WDR5還元後に分析されました.
主要な成果:
- NONOはPER1関連因子として特定され,PERの活性を調節する.
- NONO発現の減少は,哺乳類の細胞の昼夜リズムを弱め,果物ハエのほぼ不律性につながった.
- ヒストンメチルトランスフェラーゼ複合体の成分であるWDR5は,PER媒介による転写抑制を強化した.
- WDR5の減少は,時計遺伝子のプロモーターにおける昼間ヒストンのメチル化を減少させた.
結論:
- NONOとWDR5は,PERタンパク質の活性と表遺伝的変異に影響することで,昼夜リズムの主な調節因子である.
- これらの発見は,哺乳類の昼間時計を制御する分子機構の新しい構成要素を明らかにしています.
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