THE TRANSCRIPTION FACTOR GATA-1 REGULATES THE PROMOTER ACTIVITY OF THE PLATELET GLYCOPROTEIN-IIB GENE

Glycoprotein IIb (GPIIb) is an early and specific marker of the megaka ryocytic lineage. We have previously shown that a fragment extending 6 43 base pairs upstream the transcription start site of the human GPIIb promoter was able to control the tissue-specific expression of the CA T -gene in transfection experiments. Four potential GATA-binding sites , located at positions -463, -376, -243, and -54 are present within th is fragment. Gel shift analysis revealed that nuclear extracts from th e erythroleukemic cell line HEL contain a DNA-binding protein that rec ognizes these GATA sites. Using an antiserum raised to an hydrophilic region of the transcription factor GATA-1, the HEL GATA-binding protei n was found to be GATA-1. Point mutations of the different GATA sites indicated that they did not equally contribute to GPIIb promoter activ ity. The -463 GATA motif located in an enhancer region is essential fo r full transcription activity and was found to be dominant upon the ot her GATA motifs. When this site is mutated, the -54 GATA site appears to be essential for the remaining CAT activity. These results indicate that the transcription factor GATA-1 plays an important role in the r egulation of the transcription of the megakaryocyte specific GPIIb gen e.