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Structures of H2A.Z-associated human chromatin remodelers SRCAP and TIP60 reveal divergent mechanisms of chromatin engagement.

ABSTRACT: H2A.Z is a conserved histone variant that is localized to specific genomic regions where it plays important roles in transcription, DNA repair, and replication. Central to the biochemistry of human H2A.Z are the SRCAP and TIP60 chromatin remodelers, homologs of yeast SWR1 which catalyzes ATP-dependent H2A.Z exchange. Here, we use cryo-electron microscopy to resolve six structural states of the native SRCAP complex, uncovering conformational intermediates interpreted as a stepwise path to full nucleosome engagement. We also resolve the structure of the native TIP60 complex which consists of a structured core from which flexibly tethered chromatin binding domains emerge. Despite the shared subunit composition, the core of TIP60 displays divergent architectures from SRCAP that structurally disfavor nucleosome engagement, suggesting a distinct biochemical function.

SUBMITTER: Park G

PROVIDER: S-EPMC11312561 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Structures of H2A.Z-associated human chromatin remodelers SRCAP and TIP60 reveal divergent mechanisms of chromatin engagement.

Park Giho G Patel Avinash B AB Wu Carl C Louder Robert K RK

bioRxiv : the preprint server for biology 20240730

H2A.Z is a conserved histone variant that is localized to specific genomic regions where it plays important roles in transcription, DNA repair, and replication. Central to the biochemistry of human H2A.Z are the SRCAP and TIP60 chromatin remodelers, homologs of yeast SWR1 which catalyzes ATP-dependent H2A.Z exchange. Here, we use cryo-electron microscopy to resolve six structural states of the native SRCAP complex, uncovering conformational intermediates interpreted as a stepwise path to full nu ...[more]

PMID: 39131301

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