ヒストン脱酸化酵素3によって調整される昼夜リズムが,肝臓の脂質代謝を制御する
1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Science (New York, N.Y.)
|March 12, 2011
まとめ
肝臓におけるヒストン脱酸化酵素3 (HDAC3) の昼夜リズムは,代謝の健康にとって極めて重要です. Rev-erbαによって調節されるその徴募は,脂質代謝を制御し,肝臓ステアトーシスを予防します.
科学分野:
- 分子生物学は分子生物学である.
- クロノバイオロジーはクロノバイオロジーを用います.
- メタボリック疾患
背景:
- シルカディアンクロックの障害は,肥満や糖尿病などの代謝疾患を悪化させます.
- ヒストン脱酸化酵素3 (HDAC3) は,遺伝子発現を調節する役割を果たします.
研究 の 目的:
- ネズミの肝臓におけるHDAC3の徴募の昼夜リズムを調査する.
- 肝臓の脂質代謝とホメオスタシスにおけるHDAC3とRev-erbαの役割を理解する.
主な方法:
- サーカディアンリズム分析を用いてマウス肝臓のゲノムにHDAC3の採用を研究した.
- ヒストンアセチル化とHDAC3結合の関係を調査した.
- 代謝遺伝子の近くのRev-erbαとHDAC3のコロカライゼーションを調べました.
- 肝臓の脂質代謝に対するHDAC3またはRev-erbα消去の影響を評価した.
主要な成果:
- マウスの肝臓におけるHDAC3ゲノムリクルートメントは,ヒストンのアセチル化と逆相関する昼夜リズムを示しています.
- このリズムは,日中核受容体Rev-erbα. に依存しています.
- HDAC3とRev-erbαは,脂質代謝に関与する遺伝子の近くでコロカライズされます.
- HDAC3またはRev-erbαの削除は,肝硬化症 (脂肪肝疾患) を引き起こします.
結論:
- Rev-erbαによるHDAC3のゲノムリクルートにより,ヒストンアセチル化の昼夜リズムが確立されます.
- このリズムは,遺伝子発現の調節と正常な肝臓脂質ホメオスタシスの維持に不可欠です.
- 異常なHDAC3-Rev-erbα相互作用は,脂質代謝を乱し,代謝疾患に寄与する.
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