The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation
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.
|Keywords||ChIP sequencing, Development, Differentiation, Erythropoiesis, Long-range interactions, Transcription factor complexes|
|Persistent URL||dx.doi.org/10.1101/gad.551810, hdl.handle.net/1765/28059|
|Journal||Genes & Development|
|Note||Free full text at PubMed|
Soler, E, Andrieu-Soler, C, de Boer, E, Bryne, J.C, Thongjuea, S, Stadhouders, R, … Grosveld, F.G. (2010). The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation. Genes & Development, 24(3), 277–289. doi:10.1101/gad.551810