昼間の時計のネガティブなフィードバックのための分子機構
Hao A Duong1, Maria S Robles, Darko Knutti
1Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|June 18, 2011
まとめ
哺乳類の昼夜リズムはPERIOD (PER) タンパク質に依存しています. この研究では,PSFとSIN3Aを含むPER複合体が,ヒストン脱酸化酵素を勧誘してPer1の転写を抑制し,重要な負のフィードバックメカニズムを解明する方法を明らかにしました.
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.
- エピジェネティクス エピジェネティクス
背景:
- 哺乳類の昼夜リズムは,CLOCK-BMAL1およびPERIOD (PER) タンパク質を含む分子フィードバックループによって調節されます.
- ユカリオットの日中時計における負のフィードバックの正確な分子機構は,ほとんど不明のままである.
研究 の 目的:
- 哺乳類の昼間時計における負のフィードバックの基礎となる分子機構を解明する.
- PER複合体のタンパク質構成要素とそのトランスクリプション抑制における役割を特定する.
主な方法:
- マウス組織からのPERタンパク質複合体の浄化と分析.
- 関連するタンパク質の識別,PSF (ポリピリミジン経路結合タンパク質関連スプライシング因子) を含む.
- SIN3AとヒストンデセチラゼのPer1プロモーターへの徴用を調査する.
主要な成果:
- PSFはPER複合体の構成要素として特定されました.
- PER複合体内のPSFは,転写阻害複合体の支架であるSIN3Aを勧誘する.
- PER複合体はリズム的にヒストン脱エチラゼをPer1プロモーターに提供し,Per1の転写を抑制します.
結論:
- PER複合体は,PSFとSIN3Aを通して,昼間の時計の負のフィードバックのための分子機構を提供します.
- この研究は,表遺伝的改変を介して日中の遺伝子発現を調節するPER複合体の新しい機能を特定しています.
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