The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation
| Autor: | Christine Steinhoff, Mary Stevens, Erikjan Rijkers, Christel E M Kockx, Jan Christian Bryne, Jun Hou, Frank Grosveld, Boris Lenhard, Robert-Jan Palstra, Supat Thongjuea, Wilfred F. J. van IJcken, Ralph Stadhouders, Ernie de Boer, Eric Soler, Charlotte Andrieu-Soler |
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| Přispěvatelé: | Cell biology, Biochemistry, Clinical Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
transcription factor complexes
Cellular differentiation Biology Development Chromosome conformation capture Mice Erythroid Cells ChIP sequencing Genetics Tumor Cells Cultured Animals Binding site Promoter Regions Genetic Transcription factor long-range interactions Binding Sites Genome Activator (genetics) Promoter Cell Differentiation LIM Domain Proteins Cell biology ChIP-sequencing DNA-Binding Proteins Differentiation erythropoiesis Developmental Biology TAL1 Transcription Factors Research Paper |
| Zdroj: | Genes & Development, 24(6), 277-289. Cold Spring Harbor Laboratory Press Genes & Development Genes and Development, 24(6). Cold Spring Harbor Laboratory Press |
| ISSN: | 1549-5477 0890-9369 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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