ALTERNATIVE PROMOTERS REGULATE TRANSCRIPTION OF THE MOUSE GATA-2 GENE

Transcription factor GATA-2 has been shown to be a key regulator in he matopoietic progenitor cells, To elucidate how the expression of the G ATA-2 gene is controlled, we isolated the mouse GATA-2 (mGATA-2) gene. Transcription of mGATA-2 mRNAs was found to initiate from two distinc t first exons, both of which encode entirely untranslated regions, whi le the remaining five exons are shared by each of the two divergent mR NAs. Reverse transcriptase-polymerase chain reaction analysis revealed that GATA-2 mRNA initiated at the upstream first exon (IS) in Sca-1()/c-kit(+) hematopoietic progenitor cells, whereas mRNA that initiates at the downstream first exon (IG) is expressed in all tissues and cel l lines that express GATA-2. While the structure of the IG exon/promot er shows high similarity to those of the Xenopus and human GATA-2 gene s, the IS exon/promoter has not been described previously, When we exa mined the regulation contributing to IS transcription using transient transfection assays, we found that sequences lying between -79 and -61 are critical for the cell type-specific activity of the IS promoter, DNase I footprinting experiments and electrophoretic mobility shift as says demonstrated the binding of transcription factors to this region, These data indicate that the proximal 80 base pair region of IS promo ter is important for the generation of cell type-specific expression o f mGATA-2 from the IS exon.