AN UPSTREAM, DNASE-I HYPERSENSITIVE REGION OF THE HEMATOPOIETIC-EXPRESSED TRANSCRIPTION FACTOR GATA-1 GENE CONFERS DEVELOPMENTAL SPECIFICITY IN TRANSGENIC MICE

The transcription factor GATA-1, which is expressed in several hematop oietic lineages and multipotential progenitors, is required for the de velopment of red blood cells and platelets. To identify control elemen ts of the mouse GATA-1 gene, se analyzed DNase I hypersensitivity of t he locus in erythroid chromatin and the expression of GATA-1/Escherich ia coli beta-galaclosidase (lacZ) transgenes in mice, Transgenes with 2.7 kb of promoter sequences are expressed infrequently and only withi n adult (definitive) erythroid cells, We show that inclusion of an ups tream hypersensitive site (HS I) markedly enhances the frequency of ex pressing transgenic lines and activates expression in primitive erythr oid cells. This pattern recapitulates the proper pattern of GATA-1 exp ression during development, By breeding a GATA-1/lacZ transgene into a GATA-1(-) background, we also have shown that the activation or maint enance of GATA-1 expression does not require the presence of GATA-1 it self, thereby excluding simple models of positive autoregulation, The transgene cassette reported here should be useful in directing express ion of foreign sequences at the onset of hematopoiesis in the embryo a nd mag assist in the identification of upstream regulators of the GATA -1 gene.