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

Luigi LerraMartina PanattaDominik BärIsabella ZaniniJennifer Yihong TanAgnese PisanoChiara MungoCélia BarouxVikram Govind PanseAna C MarquesRaffaella Santoro
Published in: Molecular cell (2024)
The nucleus is composed of functionally distinct membraneless compartments that undergo phase separation (PS). However, whether different subnuclear compartments are connected remains elusive. We identified a type of nuclear body 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-body disruption promotes BAZ2A invasion into H3K27me3 domains, causing H3K27me3-body loss and gene upregulation. Weak BAZ2A-RNA interactions, such as with nascent transcripts, promote BAZ2A bodies, whereas the strong binder long non-coding RNA (lncRNA) Malat1 impairs them while mediating BAZ2A association to chromatin at nuclear speckles. In addition to unraveling 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.
Keyphrases
  • gene expression
  • long non coding rna
  • genome wide
  • transcription factor
  • dna damage
  • poor prognosis
  • dna methylation
  • nucleic acid
  • oxidative stress