Published in
Cold Spring Harbor Laboratory Press, Genes & Development, 3(24), p. 277-289, 2010
DOI: 10.1101/gad.551810
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The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation
,
Charlotte Andrieu-Soler,
Ernie de Boer,
Jan Christian Bryne,
Supat Thongjuea,
Ralph Stadhouders,
Robert-Jan Palstra ,
Mary Stevens,
Christel Kockx ,
Wilfred van IJcken ,
Jun Hou,
Christine Steinhoff,
Erikjan Rijkers,
Boris Lenhard ,
Frank Grosveld
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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.