mSin3Aによる完全な転写抑制にはヒストン脱酸化酵素の活性が必要である
C A Hassig1, T C Fleischer, A N Billin
1Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Cell
|May 2, 1997
まとめ
Mad:Maxタンパク質は,mSin3Aコアプレッサーを介して転写を抑制する. これらの複合体はヒストン脱酸化酵素の活性を示しており,ヒストンの脱酸化がMad-Max-mSin3A媒介による転写抑制の鍵であることを示唆しています.
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
- タンパク質生化学 タンパク質生化学
背景:
- マッドファミリータンパク質は,マックスと異体化して,転写を抑制する.
- Mad:Maxによる転写抑制には,コアプレッサーmSin3AまたはmSin3Bが含まれています.
- mSin3Aは,多タンパク質複合体の一部であることが知られている.
研究 の 目的:
- mSin3Aを含む複合体のインビボ組成を調べるため.
- mSin3A複合体がヒストン脱酸化酵素活性を持っているかどうかを判断する.
- Mad-Max-mSin3A媒介による転写抑制におけるヒストン脱酸化の役割を明らかにする.
主な方法:
- 細胞抽出物からmSin3Aの免疫プレシピテーション.
- 関連するポリペプチドをタンパク質ゲル電泳法で分析する.
- mSin3A免疫複合体におけるヒストン脱酸化酵素の活性に関する測定.
- 転写抑制を評価するためのレポーター遺伝子解析.
主要な成果:
- mSin3Aは,大型で異質な多タンパク質複合体の一部として,in vivoに存在します.
- 少なくとも7つのポリペプチドが,mSin3A.と密接かつ特異的に関連している.
- 2つのmSin3A関連タンパク質 (p50,p55) はヒストン脱酸化酵素HDAC1.1と関連している.
- mSin3A免疫複合体は,トラポキシンに敏感なヒストン脱酸化酵素の重要な活性を示しています.
- トラポキシン治療は,レポーター遺伝子のmSin3A媒介抑制を減少させます.
結論:
- mSin3Aはヒストン脱酸化酵素活性を持つ大型マルチタンパク質複合体の成分です.
- ヒストンの脱酸化は,Mad-Max-mSin3A複合体による転写抑制のメカニズムとして関与しています.
関連する概念動画
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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...