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An RNA-dependent and phase-separated active subnuclear compartment safeguards repressive chromatin domains

ABSTRACT: The nucleus is composed of functionally distinct membrane-less compartments which undergo phase separation (PS). However, whether different subnuclear compartments are connected remain elusive. We identified a type of nuclear bodies with PS features composed of BAZ2A that associates with active chromatin. BAZ2A-bodies depend on RNA transcription and BAZ2A non-disordered RNA-binding TAM domain. Although BAZ2A and H3K27me3 occupancies anticorrelate in the linear genome, in the nuclear space BAZ2A-bodies contact H3K27me3-bodies. BAZ2A-bodies disruption promotes BAZ2A invasion into H3K27me3-domains, causing H3K27me3-bodies loss and gene upregulation. Weak BAZ2A-RNA interactions, such as with nascent transcripts, promote BAZ2A-bodies whereas the strong binder lncRNA Malat1 impairs them while mediating BAZ2A association to chromatin at nuclear speckles. In addition to unravelling a direct connection between nuclear active and repressive compartments through PS mechanisms, the results also showed that the strength of RNA-protein interactions regulates this process contributing to nuclear organization and the regulation of chromatin and gene expression.

ORGANISM(S): Mus musculus

PROVIDER: GSE225898 | GEO | 2024/04/09

REPOSITORIES: GEO

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