GATA-1 forms distinct activating and repressive complexes in erythroid cells.
EMBO Journal , Volume 24 - Issue 13 p. 2354- 2366
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.
|Animals, Basic Helix-Loop-Helix Transcription Factors, Carrier Proteins/genetics/metabolism, Cells, Cultured, DNA-Binding Proteins/genetics/*metabolism, Erythroid Cells/*metabolism, Erythroid-Specific DNA-Binding Factors, GATA1 Transcription Factor, Hela Cells, Histone Deacetylases/genetics/metabolism, Humans, Mice, Nuclear Proteins/genetics/metabolism, Protein Binding, Proto-Oncogene Proteins/genetics/metabolism, Repressor Proteins/genetics/*metabolism, Transcription Factors/genetics/*metabolism, Transcription, Genetic, Zinc Fingers|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Rodrigues, P.M.M, Bonte, E, Krijgsveld, J, Kolodziej, K.E, Guyot, B, Heck, A.J.R, … Strouboulis, J. (2005). GATA-1 forms distinct activating and repressive complexes in erythroid cells. EMBO Journal, 24(13), 2354–2366. doi:10.1038/sj.emboj.7600702