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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_7E94B9835811
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
An RNA-dependent and phase-separated active subnuclear compartment safeguards repressive chromatin domains.
Journal
Molecular cell
Author(s)
Lerra L., Panatta M., Bär D., Zanini I., Tan J.Y., Pisano A., Mungo C., Baroux C., Panse V.G., Marques A.C., Santoro R.
ISSN
1097-4164 (Electronic)
ISSN-L
1097-2765
Publication state
Published
Issued date
02/05/2024
Peer-reviewed
Oui
Volume
84
Number
9
Pages
1667-1683.e10
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
12/04/2024 11:16
Last modification date
11/05/2024 7:58
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