During transcription, RNA polymerase II traverses through chromatin, and post-translational modifications including histone methylations mark regions of active transcription. Histone protein H3 lysine 36 trimethylation (H3K36me3), which is established by the histone methyltransferase SETD2, suppresses cryptic transcription, regulates splicing, and serves as a binding site for transcription elongation factors. The mechanism by which the transcription machinery coordinates the deposition of H3K36me3 is not well understood. Here we provide cryo-electron microscopy structures of mammalian RNA polymerase II-DSIF-SPT6-PAF1c-TFIIS-IWS1-SETD2-nucleosome elongation complexes, revealing that the transcription machinery regulates H3K36me3 deposition by SETD2 on downstream and upstream nucleosomes. SPT6 binds the exposed H2A–H2B dimer during transcription and the SPT6 death-like domain mediates an interaction with SETD2 bound to a nucleosome upstream of RNA polymerase II.

中文翻译：

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染色质转录过程中 SETD2 H3K36 三甲基化的结构基础


在转录过程中，RNA 聚合酶 II 穿过染色质，包括组蛋白甲基化在内的翻译后修饰标记活性转录区域。组蛋白 H3 赖氨酸 36 三甲基化 （H3K36me3） 由组蛋白甲基转移酶 SETD2 建立，抑制隐蔽转录，调节剪接，并作为转录延伸因子的结合位点。转录机制协调 H3K36me3 沉积的机制尚不清楚。在这里，我们提供了哺乳动物 RNA 聚合酶 II-DSIF-SPT6-PAF1c-TFIIS-IWS1-SETD2-核小体延伸复合物的冷冻电子显微镜结构，揭示了转录机制通过 SETD2 在下游和上游核小体上调节 H3K36me3 沉积。SPT6 在转录过程中结合暴露的 H2A-H2B 二聚体，SPT6 死亡样结构域介导与结合到 RNA 聚合酶 II 上游核小体的 SETD2 的相互作用。