Structure of H3K36-methylated nucleosome-PWWP complex reveals multivalent cross-gyre binding

被引:57
|
作者
Wang, Haibo [1 ]
Farnung, Lucas [1 ]
Dienemann, Christian [1 ]
Cramer, Patrick [1 ]
机构
[1] Max Planck Inst Biophys Chem, Dept Mol Biol, Gottingen, Germany
基金
欧洲研究理事会;
关键词
NOVO DNA METHYLTRANSFERASES; HISTONE H3; MOLECULAR-BASIS; H3K36ME3; RECOGNITION; CHROMATIN-STRUCTURE; TUDOR DOMAIN; CRYO-EM; TRANSCRIPTION; LEDGF/P75; IDENTIFICATION;
D O I
10.1038/s41594-019-0345-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-angstrom 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.
引用
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页码:8 / +
页数:16
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