Three-dimensional chromatin reorganization regulates B cell development during ageing.
Nat Cell Biol
; 26(6): 991-1002, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38866970
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Envejecimiento
/
Linfocitos B
/
Cadenas Pesadas de Inmunoglobulina
/
Linfopoyesis
/
Ensamble y Desensamble de Cromatina
Límite:
Animals
Idioma:
En
Revista:
Nat Cell Biol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos