An RNA-dependent and phase-separated active subnuclear compartment safeguards repressive chromatin domains.
Détails
Télécharger: 38599210.pdf (7721.53 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_7E94B9835811
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
An RNA-dependent and phase-separated active subnuclear compartment safeguards repressive chromatin domains.
Périodique
Molecular cell
ISSN
1097-4164 (Electronic)
ISSN-L
1097-2765
Statut éditorial
Publié
Date de publication
02/05/2024
Peer-reviewed
Oui
Volume
84
Numéro
9
Pages
1667-1683.e10
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
Mots-clé
Chromatin/metabolism, Chromatin/genetics, RNA, Long Noncoding/genetics, RNA, Long Noncoding/metabolism, Humans, Histones/metabolism, Histones/genetics, Cell Nucleus/metabolism, Cell Nucleus/genetics, RNA-Binding Proteins/metabolism, RNA-Binding Proteins/genetics, HeLa Cells, Transcription, Genetic, RNA/metabolism, RNA/genetics, Animals, Gene Expression Regulation, BAZ2A, H3K27me3, Malat1, RNA, chromatin, ground-state pluripotency, nuclear condensates, nuclear speckles, phase separation
Pubmed
Open Access
Oui
Création de la notice
12/04/2024 11:16
Dernière modification de la notice
11/05/2024 7:58