The kidney-expressed winged helix transcription factor FREAC-4 is regulated by Ets-1 -: A possible role in kidney development

In this paper we show that the kidney-expressed winged helix transcription factor FREAC-4 is regulated by Ets-l, another kidney-expressed transcription factor. Through transfection experiments three Ets-l cis-elements are identified within the first 152 nucleotides upstream of the transcription start in the freac-4 promoter. These sites are confirmed in a DNase I in vitro protection assay using recombinant Ets-l protein. In cotransfection experiments using an Ets-l expression vector, the induction of freac-4 reporter gene activity is attenuated approximately B-fold when the three Ets-l binding sites are mutated. Furthermore, we demonstrate that overexpression of Ets-l in the human embryonic kidney cell line 293 is sufficient to increase freac-4 mRNA levels. These results are compatible with the hypothesis that Ets-l acts as an upstream regulator of FREAC-4 expression during kidney development.