Article
- The EMBO Journal (2005) 24, 2354 - 2366
- doi:10.1038/sj.emboj.7600702
Published online: 26 May 2005
Subject Category:
GATA-1 forms distinct activating and repressive complexes in erythroid cells
Patrick Rodriguez1, Edgar Bonte1, Jeroen Krijgsveld2, Katarzyna E Kolodziej1, Boris Guyot3, Albert JR Heck2, Paresh Vyas3, Ernie de Boer1, Frank Grosveld1 and John Strouboulis1
- Department of Cell Biology, Erasmus University Medical Center, Rotterdam, The Netherlands
- Department of Biomolecular Mass Spectrometry, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
- Department of Haematology, The Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
Correspondence to:
John Strouboulis, Department of Cell Biology, Erasmus University Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands. Tel.: + 31 10 408 7352; Fax: + 31 10 408 9768; E-mail: i.strouboulis@erasmusmc.nl
Received 11 November 2004; Accepted 3 May 2005
Abstract
GATA-1 is essential for the generation of the erythroid, megakaryocytic, eosinophilic and mast cell lineages. It acts as an activator and repressor of different target genes, for example, in erythroid cells it represses cell proliferation and early hematopoietic genes while activating erythroid genes, yet it is not clear how both of these functions are mediated. Using a biotinylation tagging/proteomics approach in erythroid cells, we describe distinct GATA-1 interactions with the essential hematopoietic factor Gfi-1b, the repressive MeCP1 complex and the chromatin remodeling ACF/WCRF complex, in addition to the known GATA-1/FOG-1 and GATA-1/TAL-1 complexes. Importantly, we show that FOG-1 mediates GATA-1 interactions with the MeCP1 complex, thus providing an explanation for the overlapping functions of these two factors in erythropoiesis. We also show that subsets of GATA-1 gene targets are bound in vivo by distinct complexes, thus linking specific GATA-1 partners to distinct aspects of its functions. Based on these findings, we suggest a model for the different roles of GATA-1 in erythroid differentiation.
Keywords:
- chromatin,
- GATA-1,
- hematopoiesis,
- repression,
- transcription factors
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