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Multivalent histone and DNA engagement by the triple reader module of ZMYND8 directs the recruitment of a transcriptional network to genes to regulate gene expression

ABSTRACT: Elucidation of multivalent interactions involving both DNA and histone post-translational-modifications (PTMs) is essential for providing insight into complex biological functions. We report here the high resolution crystal structure of the N-terminal triple reader module (PHD-Bromo-PWWP) of ZMYND8, which forms a stable unit, capable of simultaneously recognizing histone PTMs and providing a charged platform for DNA interaction. Monte Carlo simulations provide a model whereby the reader module directly engages the core nucleosome particle, extracting the entire histone H3 tail and initiating contacts with the DNA super-coil structure. Systematic mutation of these interaction interfaces reveals cooperativity within the ensemble. Single domain disruption destroys the functional network of interactions initiated by ZMYND8, which impairs recruitment to sites of DNA damage and alters transcription. Taken together, our results establish an important role of the ZMYND8 multivalent reader module in nucleosome binding and chromatin function.

ORGANISM(S): Homo sapiens

PROVIDER: GSE75624 | GEO | 2021/04/30

REPOSITORIES: GEO

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Multivalent histone and DNA engagement by a PHD/BRD/PWWP triple reader cassette recruits ZMYND8 to K14ac-rich chromatin

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