Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation.
Nat Immunol
; 19(9): 932-941, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-30127433
ABSTRACT
Cohesin is important for 3D genome organization. Nevertheless, even the complete removal of cohesin has surprisingly little impact on steady-state gene transcription and enhancer activity. Here we show that cohesin is required for the core transcriptional response of primary macrophages to microbial signals, and for inducible enhancer activity that underpins inflammatory gene expression. Consistent with a role for inflammatory signals in promoting myeloid differentiation of hematopoietic stem and progenitor cells (HPSCs), cohesin mutations in HSPCs led to reduced inflammatory gene expression and increased resistance to differentiation-inducing inflammatory stimuli. These findings uncover an unexpected dependence of inducible gene expression on cohesin, link cohesin with myeloid differentiation, and may help explain the prevalence of cohesin mutations in human acute myeloid leukemia.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Células-Tronco Hematopoéticas
/
Proteínas Nucleares
/
Proteínas Cromossômicas não Histona
/
Leucemia Mieloide Aguda
/
Diferenciação Celular
/
Proteínas de Ciclo Celular
/
Autorrenovação Celular
/
Macrófagos
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Reino Unido