GATA-1 TRANSCRIPTION IS CONTROLLED BY DISTINCT REGULATORY MECHANISMS DURING PRIMITIVE AND DEFINITIVE ERYTHROPOIESIS

Transcription factor GATA-1 is required for the terminal differentiati on of both the primitive and definitive erythroid cell lineages, and y et the regulatory mechanisms of GATA-1 itself are not well understood. To clarify how the GATA-1 gene is transcriptionally controlled in viv o, presumptive regulatory regions of the gene were tested by fusion to a reporter gene and then examined in transgenic mice. We found that a transcriptional control element located between -3.9 and -2.6 kb 5' t o the erythroid first exon serves as an activating element and that th is sequence alone is sufficient to recapitulate the expression of GATA -1 (but uniquely in primitive erythroid cells), Addition of sequences from the GATA-1 first intron to this upstream element provides a neces sary and sufficient condition for complete recapitulation of GATA-1 ex pression in both primitive and definitive erythroid cells. The first i ntron element does not possess intrinsic transcriptional activation po tential when linked to the GATA-1 gene promoter but rather requires th e upstream activating element for its activity, These experiments show that GATA-1 gene expression is regulated by discrete transcriptional control elements during definitive and primitive erythropoiesis: The 5 ' element displays properties anticipated for a primitive erythroid ce ll-specific activating element, and the novel element within the GATA- 1 first intron specifically augments this activity in definitive eryth roid cells.