In this paper we show that the kidney-expressed winged helix transcription factor FREAC-4 is regulated by Ets-1, another kidney-expressed transcription factor. Through transfection experiments three Ets-1 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-1 protein. In cotransfection experiments using an Ets-1 expression vector, the induction of freac-4 reporter gene activity is attenuated approximately 6-fold when the three Ets-1 binding sites are mutated. Furthermore, we demonstrate that overexpression of Ets-1 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-1 acts as an upstream regulator of FREAC-4 expression during kidney development.
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Cederberg et al. (1999) studied this question.