Recognition of histone-modified nucleosomes by specific reader domains underlies the regulation of chromatin-associated processes. Whereas structural studies revealed how reader domains bind modified histone peptides, it is unclear how reader domains interact with modified nucleosomes. Here, we report the cryo-electron microscopy structure of the PWWP reader domain of human transcriptional coactivator LEDGF in complex with an H3K36-methylated nucleosome at 3.2-Å resolution. The structure reveals multivalent binding of the reader domain to the methylated histone tail and to both gyres of nucleosomal DNA, explaining the known cooperative interactions. The observed cross-gyre binding may contribute to nucleosome integrity during transcription. The structure also explains how human PWWP domain-containing proteins are recruited to H3K36-methylated regions of the genome for transcription, histone acetylation and methylation, and for DNA methylation and repair.

中文翻译：

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H3K36-甲基化核小体-PWWP 复合物的结构揭示了多价交叉环流结合。

特定阅读器结构域对组蛋白修饰核小体的识别是染色质相关过程调节的基础。虽然结构研究揭示了阅读域如何结合修饰的组蛋白肽，但尚不清楚阅读域如何与修饰的核小体相互作用。在这里，我们报告了人类转录共激活因子 LEDGF 的 PWWP 阅读器结构域与 H3K36 甲基化核小体复合的低温电子显微镜结构，分辨率为 3.2-Å。该结构揭示了阅读器结构域与甲基化组蛋白尾和核小体 DNA 的两个环的多价结合，解释了已知的协同相互作用。观察到的交叉环流结合可能有助于转录过程中的核小体完整性。