Journal
GENES & DEVELOPMENT
Volume 24, Issue 3, Pages 277-289Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.551810
Keywords
ChIP sequencing; transcription factor complexes; development; differentiation; erythropoiesis; long-range interactions
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Funding
- NIH
- Cells into Organs
- EuTRACC consortium
- Marie Curie fellowships
- NBIC
- Norwegian Research Council (YFF)
- Bergen Research Foundation
- Netherlands Organisation for Scientific Research (NWO) [700.57.408]
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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.
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