Three-dimensional chromatin reorganization regulates B cell development during ageing.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
12 Jun 2024
12 Jun 2024
Historique:
received:
01
11
2022
accepted:
16
04
2024
medline:
13
6
2024
pubmed:
13
6
2024
entrez:
12
6
2024
Statut:
aheadofprint
Résumé
The contribution of three-dimensional genome organization to physiological ageing is not well known. Here we show that large-scale chromatin reorganization distinguishes young and old bone marrow progenitor (pro-) B cells. These changes result in increased interactions at the compartment level and reduced interactions within topologically associated domains (TADs). The gene encoding Ebf1, a key B cell regulator, switches from compartment A to B with age. Genetically reducing Ebf1 recapitulates some features of old pro-B cells. TADs that are most reduced with age contain genes important for B cell development, including the immunoglobulin heavy chain (Igh) locus. Weaker intra-TAD interactions at Igh correlate with altered variable (V), diversity (D) and joining (J) gene recombination. Our observations implicate three-dimensional chromatin reorganization as a major driver of pro-B cell phenotypes that impair B lymphopoiesis with age.
Identifiants
pubmed: 38866970
doi: 10.1038/s41556-024-01424-9
pii: 10.1038/s41556-024-01424-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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