Key regulators control distinct transcriptional programmes in blood progenitor and mast cells.
EMBO J
; 33(11): 1212-26, 2014 Jun 02.
Article
em 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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
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Fatores de Transcrição
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Transcrição Gênica
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Regulação da Expressão Gênica
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Mastócitos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article