Key regulators control distinct transcriptional programmes in blood progenitor and mast cells.
EMBO J
; 33(11): 1212-26, 2014 Jun 02.
Article
en En
| MEDLINE
| ID: mdl-24760698
ABSTRACT
Despite major advances in the generation of genome-wide binding maps, the mechanisms by which transcription factors (TFs) regulate cell type identity have remained largely obscure. Through comparative analysis of 10 key haematopoietic TFs in both mast cells and blood progenitors, we demonstrate that the largely cell type-specific binding profiles are not opportunistic, but instead contribute to cell type-specific transcriptional control, because (i) mathematical modelling of differential binding of shared TFs can explain differential gene expression, (ii) consensus binding sites are important for cell type-specific binding and (iii) knock-down of blood stem cell regulators in mast cells reveals mast cell-specific genes as direct targets. Finally, we show that the known mast cell regulators Mitf and c-fos likely contribute to the global reorganisation of TF binding profiles. Taken together therefore, our study elucidates how key regulatory TFs contribute to transcriptional programmes in several distinct mammalian cell types.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre
/
Factores de Transcripción
/
Transcripción Genética
/
Regulación de la Expresión Génica
/
Mastocitos
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
EMBO J
Año:
2014
Tipo del documento:
Article