据了解，在转录过程中，RNA聚合酶II穿过染色质，翻译后修饰包括组蛋白甲基化标记了活跃转录区域。组蛋白H3赖氨酸36三甲基化（H3K36me3）是由组蛋白甲基转移酶SETD2建立的，它抑制隐转录，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。
研究小组提供了哺乳动物RNA聚合酶II-DSIF-SPT6-PAF1c-TFIIS-IWS1-SETD2-核小体延伸复合物的低温电镜结构，揭示了转录机制调节SETD2在下游和上游核小体上的H3K36me3沉积。SPT6在转录过程中与暴露的H2A-H2B二聚体结合，SPT6死亡样结构域介导与RNA聚合酶II上游核小体结合的SETD2相互作用。
附：英文原文
Title: Structural basis of H3K36 trimethylation by SETD2 during chromatin transcription
Author: Jonathan W. Markert, Jelly H. Soffers, Lucas Farnung
Issue&Volume: 2024-12-12
Abstract: 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.
DOI: adn6319
Source: https://www.science.org/doi/10.1126/science.adn6319