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The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation

2010; Cold Spring Harbor Laboratory Press; Volume: 24; Issue: 3 Linguagem: Inglês

10.1101/gad.551810

1549-5477

Éric Soler, Charlotte Andrieu‐Soler, Ernie de Boer, Jan Christian Bryne, Supat Thongjuea, Ralph Stadhouders, Robert‐Jan Palstra, Mary E. Stevens, Christel Kockx, Wilfred F. J. van IJcken, Jun Hou, Christine Steinhoff, Erikjan Rijkers, Boris Lenhard, Frank Grosveld,

Immune Cell Function and Interaction

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.