Hematopoiesis: how does it happen?

Hematopoiesis entails the generation of stem cells, the proliferation and maintenance of multipotential progenitors, and lineage commitment and maturation. During the past year, critical components of these steps have been defined. Notable are gene-targeting experiments in mice in which one or more hematopoietic lineages have been shown to be ablated upon inactivation of several nuclear regulatory proteins (GATA-2, Tal-1/SCL, Rbtn2/LMO2, PU.1, Ikaros, E2A, and Pax-5), and experiments that establish GATA-1 as a factor capable of programming at least three lineages (erythroid, thrombocytic, and eosinophilic) from a transformed avian progenitor cell.     

GATA-1 forms distinct activating and repressive complexes in erythroid cells

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.