TET2は,遺伝子転写中にヒストンO-GlcNAcylationを促進する
Qiang Chen1, Yibin Chen, Chunjing Bian
1Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Nature
|December 11, 2012
まとめ
十""の転位 (TET) 酵素が遺伝子転写を調節する. この研究では,TET2がO-リンクされたβ-N-アセチルグルコサミン (O-GlcNAc) トランスファーゼ (OGT) と相互作用することを明らかにし,TET2に依存する染色体O-GlcNAcylation機構を遺伝子調節のために発見しました.
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.
- バイオケミストリー バイオケミストリー
背景:
- 10の11の転位 (TET) 酵素 (TET1,TET2,TET3) は,5-メチルサイトシンを5-ヒドロキシメチルサイトシンに変換することによってDNAを改変します.
- TET酵素が遺伝子転写を調節する正確な分子機構は完全に理解されていません.
研究 の 目的:
- TETタンパク質の機能的パートナーを特定する.
- TET媒介による遺伝子転写調節の分子メカニズムを解明する.
主な方法:
- TETタンパク質の相互作用者を特定するためのタンパク質親和性浄化.
- TET2-OGT相互作用とそのクロマチンの関連性およびヒストンの改変への影響の分析.
- トランスクリプション開始部位におけるTET2とO-GlcNAcylationの役割を調査する.
主要な成果:
- TET2とTET3は,O-リンクされたβ-N-アセチルグルコサミン (O-GlcNAc) トランスファーゼ (OGT) と関連することが判明しました.
- TET2はOGTと直接相互作用し,OGTの染色体結合とOGT依存ヒストンO-GlcNAcylationを促進する.
- TET2とOGTは,転写開始部位で共局所化し,TET2のダウンレギュレーションは,転写に不可欠なヒストンO-GlcNAcマークに影響を与えます.
結論:
- 新しいTET2依存のクロマチンのO-GlcNAcylationが特定されました.
- TET2とOGTは,遺伝子転写を調節するために,DNAとヒストンの二重エピジェネティック変異を調整します.
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