STAT1のメチルトランスフェラーゼSETD2媒介メチル化は,インターフェロンの抗ウイルス作用に不可欠である
Kun Chen1, Juan Liu2, Shuxun Liu2
1Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
Cell
|July 29, 2017
まとめ
SETD2は,STAT1をメチル化し,IFN刺激遺伝子 (ISG) を促進することで,インターフェロン-α (IFNα) 抗ウイルス免疫を強化する. SETD2の喪失は,B型肝炎ウイルス (HBV) 感染を高め,SETD2を強調する.
科学分野:
- 免疫学
- エピジェネティクス
- ヘパトロジー
背景:
- インターフェロン-α (IFNα) 信号は,IFN刺激遺伝子 (ISG) による抗ウイルス防御に不可欠です.
- 肝炎Bウイルス (HBV) の複製はIFNαによって抑制されるが,その根底にある表遺伝的メカニズムは完全に理解されていない.
研究 の 目的:
- HBVに対するIFNα媒介抗ウイルス免疫を調節するエピジェネティック・モディファイヤーを特定する.
- SETD2がIFNαシグナル伝達とHBV複製に影響を与える分子メカニズムを解明する.
主な方法:
- IFNαで治療された細胞における711の表遺伝子変異体の高通量RNAiスクリーニング.
- 条件付きノックアウトマウスにおけるHBV複製の分析
- STAT1メチル化とH3K36トリメチル化を評価する生化学的測定法
主要な成果:
- SETD2はIFNα抗ウイルス免疫の重要な増強剤として特定されました.
- ネズミの肝細胞特異的なSetd2欠失はHBV感染の増加につながった.
- SETD2はライシン525でSTAT1を直接メチル化し,STAT1のリン酸化と抗ウイルス反応を強める.
- SETD2はISGプロモーターにおけるH3K36トリメチル化を触媒化し,遺伝子の活性化を促進する.
結論:
- SETD2によるSTAT1メチル化は,IFNα依存の抗ウイルス免疫に不可欠である.
- SETD2はウイルス感染,特にHBVの制御に重要な役割を果たします.
- SETD2は,ウイルス性肝炎の管理のための潜在的な治療目標です.
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