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.
Soler
Eric
E
Department of Cell Biology, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands. e.soler@erasmusmc.nl
Andrieu-Soler
Charlotte
C
de Boer
Ernie
E
Bryne
Jan Christian
JC
Thongjuea
Supat
S
Stadhouders
Ralph
R
Palstra
Robert-Jan
RJ
Stevens
Mary
M
Kockx
Christel
C
van Ijcken
Wilfred
W
Hou
Jun
J
Steinhoff
Christine
C
Rijkers
Erikjan
E
Lenhard
Boris
B
Grosveld
Frank
F
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
D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C102084:Ldb1 protein, mouse; D014157:Transcription Factors