title: The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation.
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.
authors.affiliation: Department of Cell Biology, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands. e.soler@erasmusmc.nl
authors.forename: Eric
authors.initials: E
authors.lastname: Soler
authors.forename: Charlotte
authors.initials: C
authors.lastname: Andrieu-Soler
authors.forename: Ernie
authors.initials: E
authors.lastname: de Boer
authors.forename: Jan Christian
authors.initials: JC
authors.lastname: Bryne
authors.forename: Supat
authors.initials: S
authors.lastname: Thongjuea
authors.forename: Ralph
authors.initials: R
authors.lastname: Stadhouders
authors.forename: Robert-Jan
authors.initials: RJ
authors.lastname: Palstra
authors.forename: Mary
authors.initials: M
authors.lastname: Stevens
authors.forename: Christel
authors.initials: C
authors.lastname: Kockx
authors.forename: Wilfred
authors.initials: W
authors.lastname: van Ijcken
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.forename: Christine
authors.initials: C
authors.lastname: Steinhoff
authors.forename: Erikjan
authors.initials: E
authors.lastname: Rijkers
authors.forename: Boris
authors.initials: B
authors.lastname: Lenhard
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism; D016678:Genome; D060588:LIM Domain Proteins; D051379:Mice; D011401:Promoter Regions, Genetic; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C102084:Ldb1 protein, mouse; D014157:Transcription Factors