The Genome-Wide Dynamics of the Binding of Ldb1 Complexes during Erythroid Differentiation.. LDB1 complexes in erythroid differentiation

One of the complexes formed by the hematopoietic transcription factor Gata1 is a complex with the Ldb1 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 we studied the dynamics of the composition of the complex, in particular the binding of the negative regulators Eto2 and Mtgr1, in the context of their genome wide targets. The results 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 net decrease in the relative binding of Eto2 and Mtgr1. A 3C/seq assay shows that the binding of the Ldb1 complex marks genomic interaction sites. 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.