ヒストンH3ライシン27脱メチラーゼは,動物の後部発達を調節する

Fei Lan¹, Peter E Bayliss, John L Rinn

¹Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.

Nature

|September 14, 2007

まとめ

ヒストンデメチラゼUTXとJMJD3は,遺伝子調節に不可欠なH3K27me3マークを除去する. 彼らの機能障害はHOX遺伝子発現と動物の発達に影響を与え,発達における保存された役割を強調しています.

科学分野:

エピジェネティクスエピジェネティクス
発達生物学発達生物学とは
分子生物学は分子生物学である.

背景:

ヒストンのメチル化ダイナミクスは,遺伝子調節に極めて重要です.
ヒストンH3K27トリメチル化 (H3K27me3) は,遺伝子サイレンス,発達パターン,幹細胞同一性に関与しています.
EZH2過剰発現に関連した異常なH3K27メチル化が,がんに関与している.

研究の目的:

H3K27me3の脱メチル化におけるJmjCドメインを含むタンパク質UTXとJMJD3の役割を調査する.
HOX遺伝子発現の調節におけるUTXの機能と,動物の発達に対するその影響について調べる.

主な方法:

H3K27me3/2.2.3に対するUTXとJMJD3の脱メチラゼ活性を示すための生化学的分析.
クロマチン免疫プレシピテーションは,HOX遺伝子ロシエーションでのUTX濃縮を評価するためのものです.
人間の細胞におけるRNA干渉とゼブラフィッシュにおけるモルフォリノベースのノックダウンで,遺伝子調節と発達障害を研究する.

主要な成果:

UTXとJMJD3は,H3K27me3/2デメチラゼとして特定されました.
UTXの局所化は,ESCと比較して,線維芽細胞におけるHOX遺伝子発現状態と相関しています.
UTXの抑制は,H3K27me3とHOX遺伝子の誤調節の増加につながった.
ゼブラフィッシュのUTXホモログの阻害は発達障害を引き起こし,機能的なヒトUTXによって部分的に救出されました.

結論:

UTXとJMJD3は,H3K27メチル化を調節する役割が保たれているH3K27デメチラゼの鍵である.
これらの酵素は,適切なHOX遺伝子発現と動物の前後部の発達に不可欠です.

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