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PMID: 20123907 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Genes & development ·Vol. 24 ·No. 3 ·2010-02-01 ·Pages 277-89

Soler E, Andrieu-Soler C, de Boer E, Bryne JC, Thongjuea S, Stadhouders R, Palstra RJ, Stevens M, Kockx C, van Ijcken W, Hou J, Steinhoff C, Rijkers E, Lenhard B, Grosveld F

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.

MeSH Terms
Animals Binding Sites Cell Differentiation DNA-Binding Proteins/genetics,metabolism Erythroid Cells/cytology,metabolism Genome LIM Domain Proteins Mice Promoter Regions, Genetic Transcription Factors Tumor Cells, Cultured
Chemicals
DNA-Binding Proteins LIM Domain Proteins Ldb1 protein, mouse Transcription Factors
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Soler Eric
Department of Cell Biology, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands. [email protected]
Andrieu-Soler Charlotte
de Boer Ernie
Bryne Jan Christian
Thongjuea Supat
Stadhouders Ralph
Palstra Robert-Jan
Stevens Mary
Kockx Christel
van Ijcken Wilfred
Hou Jun
Steinhoff Christine
Rijkers Erikjan
Lenhard Boris
Grosveld Frank
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
1549-5477
DOI
10.1101/gad.551810
Email
[email protected]
Published
2010-02-01
Pages
277-89
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2811829
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1101/gad.551810 PMC Full Text View journal details
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