GATA-1 TRANSACTIVATES THE WT1 HEMATOPOIETIC SPECIFIC ENHANCER

The Wilms' tumor gene, WT1, is believed to play a role in hematopoiesi s as it is expressed in the spleen and in immature leukemias in additi on to the developing genitourinary system. WT1 is down-regulated in di fferentiated leukemia cells both in vivo and in vitro and is upregulat ed in fetal spleen and immature leukemia cells. The modulation of WT1 expression was examined in many cell types, and a hematopoietic-specif ic enhancer element has been identified. Here we describe the transcri ptional response of this enhancer to hematopoietic-specific transcript ion factors. We found co-expression of WT1 and GATA-1 mRNA in K562 cel ls and in mouse spleen, suggesting potential interactions between thes e two transcription factors. We find that the activity of the 3' WT1 e nhancer is positively correlated with the expression of GATA-1. Gel sh ift competition experiments and transactivation studies revealed that this functional activity is mediated via binding at a GATA-binding sit e in the WT1 enhancer. The transactivation of the WT1 enhancer by GATA -1 implies that GATA-1 plays a role in the regulation of WT1 during he matopoiesis.