スフィンゴシン-1-ホスファートによる核内のヒストンアセチル化の調節
Nitai C Hait1, Jeremy Allegood, Michael Maceyka
1Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
Science (New York, N.Y.)
|September 5, 2009
まとめ
スフィンゴシン-1-ホスファート (S1P) は細胞内部で作用し,ヒストン脱酸化酵素 (HDACs) を阻害することによって遺伝子発現を調節する. この発見は,S1Pをp21やc-fos.のような遺伝子を制御するエピジェネティックメカニズムと結びつけています.
科学分野:
- 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
- バイオケミストリー バイオケミストリー
背景:
- スフィンゴシン-1-リン酸 (S1P) は,既知の細胞内機能を持つ脂質媒介体である.
- 細胞表面受容体とは無関係なS1Pの細胞内作用のメカニズムは,ほとんど不明のままである.
- スフィンゴシンキナーゼ2 (SphK2) は細胞内S1Pを生成する.
研究 の 目的:
- S1P作用の細胞内メカニズムを解明する.
- 遺伝子発現の調節におけるSphK2の役割を調査する.
- S1P.の直接的な細胞内標的を特定するために.
主な方法:
- 共同免疫プレシピテーションは,タンパク質とタンパク質の相互作用を検出するための測定法です.
- ヒストン脱酸化酵素の活性を測定するための酵素測定法.
- クロマチン免疫降水 (ChIP) は,遺伝子プロモーターの濃縮を評価する.
主要な成果:
- スフィンゴシンキナーゼ2 (SphK2) はヒストンH3と結合し,ヒストンアセチル化を調節する.
- S1Pは,ヒストン脱酸化酵素HDAC1およびHDAC2.2に直接結合し,それを阻害する.
- SphK2とS1Pは,p21とc-fos遺伝子のプロモーターで濃縮され,ヒストンのアセチル化と転写を強化します.
結論:
- ヒストン脱酸化酵素 (HDACs) は,S1Pの直接的な細胞内標的である.
- SphK2経由の核S1Pは,遺伝子発現の表遺伝的調節に役割を果たしています.
- この研究は,S1Pシグナル伝達と標的遺伝子の表遺伝子制御の間の新しい関連性を明らかにしています.
関連する概念動画
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