The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation.
Genes Dev
; 24(3): 277-89, 2010 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-20123907
ABSTRACT
One of the complexes formed by the hematopoietic transcription factor Gata1 is a complex with the Ldb1 (LIM domain-binding protein 1) and Tal1 proteins. It is known to be important for the development and differentiation of the erythroid cell lineage and is thought to be implicated in long-range interactions. Here, the dynamics of the composition of the complex-in particular, the binding of the negative regulators Eto2 and Mtgr1-are studied, in the context of their genome-wide targets. This shows that the complex acts almost exclusively as an activator, binding a very specific combination of sequences, with a positioning relative to transcription start site, depending on the type of the core promoter. The activation is accompanied by a net decrease in the relative binding of Eto2 and Mtgr1. A Chromosome Conformation Capture sequencing (3C-seq) assay also shows that the binding of the Ldb1 complex marks genomic interaction sites in vivo. This establishes the Ldb1 complex as a positive regulator of the final steps of erythroid differentiation that acts through the shedding of negative regulators and the active interaction between regulatory sequences.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Genoma
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Células Eritroides
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Proteínas de Ligação a DNA
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article