在染色体转录过程中通过SETD2进行H3K36三甲基化的结构基础
Science (New York, N.Y.)
|December 12, 2024
概括
转录机制引导基转移酶SETD2在核细胞上沉积H3K36三甲基化 (H3K36me3). 这一过程由SPT6介导,它与SETD2相互作用以调节基因转录和拼接.
科学领域:
- 分子生物学
- 表观遗传学
- 染色体生物学
背景情况:
- 在RNA聚合酶II穿越过程中标记活跃的转录部位的翻译后修饰,包括基因组甲基化.
- 素H3 lysine 36三甲基化 (H3K36me3) 对于抑制密码转录,调节拼接和招募转录延长因子至关重要.
- 通过转录机器协调H3K36me3沉积的确切机制尚不清楚.
研究的目的:
- 阐明转录机器通过SETD2协调H3K36me3的沉积机制.
- 提供RNA聚合酶II,相关因子和SETD2在转录过程中的相互作用的结构见解.
主要方法:
- 使用冷电子显微镜确定哺乳动物RNA聚合酶II延长复合物的结构.
- 这些复合体包括DSIF,SPT6,PAF1c,TFIIS,IWS1,SETD2和核细胞.
主要成果:
- 该研究揭示了转录机制如何调节SETD2对下游和上游核细胞的H3K36me3沉积.
- 在转录过程中观察到SPT6会结合暴露的H2A-H2B二元体.
- SPT6类似死亡的域与SETD2进行关键相互作用,该SETD2位于相对于RNA聚合酶II的上游核体上.
结论:
- 转录机制通过涉及SPT6和SETD2的相互作用来积极调节H3K36me3沉积.
- 这些发现为了解H3K36me3如何精确沉积以调节基因表达和染色质调节提供了结构基础.
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