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Structure of LEDGF PWWP domain bound H3K36 methylated nucleosome
Structural highlights
FunctionH32_XENLA Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Publication Abstract from PubMedRecognition 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-A 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. Structure of H3K36-methylated nucleosome-PWWP complex reveals multivalent cross-gyre binding.,Wang H, Farnung L, Dienemann C, Cramer P Nat Struct Mol Biol. 2019 Dec 9. pii: 10.1038/s41594-019-0345-4. doi:, 10.1038/s41594-019-0345-4. PMID:31819277[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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