非メチル化ヒストンH3ライシン4の認識はBHC80をLSD1媒介の遺伝子抑制とリンクする
Fei Lan1, Robert E Collins, Rossella De Cegli
1Department of Pathology, Harvard Medical School, 77 Ave Louis Pasteur, Boston, Massachusetts 02115, USA.
Nature
|August 10, 2007
まとめ
BHC80タンパク質は,遺伝子抑制におけるLSD1酵素活性に不可欠な非甲基化ヒストンH3K4を特異的に結合する. この相互作用は,表遺伝子状態と転写調節の維持に極めて重要です.
科学分野:
- エピジェネティクス エピジェネティクス
- 分子生物学は分子生物学である.
- 遺伝子規制 遺伝子規制
背景:
- ヒストンのメチル化は,クロマチンの構造と遺伝子転写を調節する.
- リスイン特異ヒストン脱メチラーゼ1 (LSD1) は,ヒストンH3を脱メチル化することによって転写を抑制する.
- BHC80 (PHF21A) は,LSD1複合体のタンパク質で,その役割は不明である.
研究 の 目的:
- LSD1複合体内のBHC80タンパク質の機能を調査する.
- BHC80のPHD指とヒストンH3の相互作用を決定する.
- LSD1媒介の転写抑制におけるBHC80の役割を明らかにする.
主な方法:
- H3ペプチドに結合したBHC80 PHD指の構造を決定するX線結晶学.
- RNA阻害 (RNAi) は,BHC80の発現を抑制する.
- 野生型および変異型BHC80の再導入
- タンパク質とクロマチンの関連性を評価するためのクロマチン免疫降水 (ChIP).
主要な成果:
- BHC80のPHD指は,H3K4me3.3.0を結合する他のPHD指とは異なり,非メチル化H3K4 (H3K4me0) を特に結合する.
- 結晶構造は,H3K4me0認識のメカニズムを明らかにした.
- BHC80ノックダウンは,LSD1標的遺伝子を抑制した.
- BHC80とLSD1は,染色体関連性において相互依存を示した.
結論:
- BHC80は,LSD1の機能と非メチル化H3K4.4の認識を組み合わせている.
- 未修正のH3K4は"ヒストンコード"の重要な構成要素として特定されています.
- 改変されていないヒストンの状態の認識は,遺伝子調節のための修正と同じくらい重要かもしれません.
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