EZH2によるB2RNAの不安定化は,ストレス反応を活性化する
Athanasios Zovoilis1, Catherine Cifuentes-Rojas1, Hsueh-Ping Chu1
1Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Cell
|December 17, 2016
まとめ
ポリコンブタンパク質EZH2とB2SINERNAはストレス遺伝子を調節する. EZH2は熱ショックでB2RNAの分解を誘発し,RNAポリメラーゼIIを通じてストレス反応性遺伝子を活性化します. これは新しいEZH2機能を明らかにします.
科学分野:
- エピジェネティクス
- 分子生物学
- ゲノミクス
背景:
- 哺乳類のゲノムの98%以上がノンコーディングであり,トランスポーザブルな要素はこのノンコーディングスペースの50%を占めています.
- 遺伝子調節における非コーディングRNAの機能は,特に転置可能な要素からの機能は,活発な研究分野である.
研究 の 目的:
- ストレス反応性遺伝子の制御における EZH2 と B2 SINE RNA の役割を調査する.
- 熱ストレスでEZH2がB2RNAと相互作用するメカニズムを解明する.
主な方法:
- 熱ショックモデルを マウス細胞で使った
- EZH2とB2RNAの相互作用を分析した.
- RNAポリメラーゼIIによる転写延長に対するB2RNAの影響を調査した.
主要な成果:
- B2RNAがストレス遺伝子に結合し,その転写を抑制することを示した.
- 熱ショックでEZH2が誘発され,B2RNAの分裂と,その後のストレス遺伝子のアップレギュレーションにつながっていることが示された.
- B2RNAをRNAポリメラーゼIIの"スピードブンプ"として識別し,熱ストレスはこの転写ブレーキを解放する.
結論:
- ヒストンメチルトランスフェラーゼの活性とは無関係なEZH2の遺伝子発現をB2RNA経由で調節する新機能が確立された.
- EZH2の遺伝子抑制と活性化の両方との関連を調整しました.
- EZH2とB2RNAが協力して 熱ストレス反応に関与する大きな遺伝子ネットワークを制御することを明らかにした.
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