ヒストンのH3.3K36M変異は,コンドロブラストーマの表層を再プログラムします

Dong Fang¹, Haiyun Gan¹, Jeong-Heon Lee²

¹Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.

Science (New York, N.Y.)

|May 28, 2016

まとめ

コンドロブラストーマのH3. 3K36M変異はヒストンのメチル化を妨害し,遺伝子発現と癌の特徴を変化させます. このエピジェネティック再プログラムが腫瘍の発達に寄与します

科学分野:

腫瘍学
エピジェネティクス
分子生物学

背景:

コンドロブラストーマはH3. 3ヒストンの変異 (H3. 3K36M) を頻繁に持ちます.
ヒストンH3ライシン36 (H3K36) メチル化は,遺伝子調節と腫瘍抑制において重要な役割を果たします.

研究の目的:

H3.3K36M変異がH3K36メチル化パターンにどのように影響するか調査する.
コンドロブラストーマにおける変化したH3K36メチル化の機能的影響を明らかにする.

主な方法:

人間の軟骨芽細胞と変異性軟骨細胞のH3K36メチル化レベルの分析
H3K36メチルトランスファーゼ (MMSETとSETD2) に対するH3.3K36Mタンパク質の影響を評価する.
H3.3K36Mコンドロサイトにおける遺伝子発現変化と癌に関連する細胞行動の評価.

主要な成果:

H3. 3K36M変異は,MMSETとSETD2を阻害することによって,H3K36メチル化を全般的に減少させる.
H3. 3K36M細胞の変異遺伝子の発現は,がん経路で強化されています.
H3. 3K36Mコンドロサイトはコロニー形成,アポトーシス抵抗,分化欠陥が増加している.

結論:

H3.3K36Mタンパク質は,H3K36メチル化パターンを再プログラムする.
この表遺伝的再プログラミングは,がんに関連した遺伝子発現を変化させ,がん細胞のフェノタイプを促進することによって,軟骨芽細胞腫瘍発生に寄与する.

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