ECTOPIC EXPRESSION OF A CONDITIONAL GATA-2 ESTROGEN-RECEPTOR CHIMERA ARRESTS ERYTHROID-DIFFERENTIATION IN A HORMONE-DEPENDENT MANNER

The GATA factors are a family of transcriptional regulatory proteins i n eukaryotes that share extensive homology in their DNA-binding domain s. One enigmatic aspect of GATA factor expression is that several GATA proteins, which ostensibly share the same DNA-binding site specificit y, are coexpressed in erythroid cells. To elucidate the roles of indiv idual GATA factors in erythropoiesis, conditional alleles of GATA-1, G ATA-2, and GATA-3 were prepared by fusing each of the factors to the h ormone-binding domain of the human estrogen receptor (ER). These GATA/ ER chimeric factors were shown to be hormone-inducible trans-activatin g proteins in transient transfection assays. When stably introduced in to primary erythroblasts or conditionally transformed erythroid progen itors cells, exogenous GATA-2/ER promoted proliferation and inhibited terminal differentiation in an estrogen-dependent manner. These phenot ypic effects are specifically attributable to the action of ectopicall y expressed GATA-2/ER because erythroblasts expressing exogenous GATA- 2 are constitutively arrested in differentiation and because erythroid progenitors expressing either Gal/ER or GATA-3/ER do not display a ho rmone-responsive block in differentiation. Thus, the GATA-2 transcript ion factor appears to play a role in regulating the self-renewal capac ity of early erythroid progenitor cells.