THE WINGED HELIX TRANSCRIPTIONAL ACTIVATOR HFH-3 IS EXPRESSED IN THE DISTAL TUBULES OF EMBRYONIC AND ADULT-MOUSE KIDNEY

The hepatocyte nuclear factor-3 (HNF-3)/fork head homolog (HFH) protei ns are an extensive family of transcription factors, which share homol ogy in the winged helix DNA binding domain. Members of the HFH/winged helix family have been implicated in cell fate determination during pa ttern formation, in organogenesis, and in cell-type-specific gene expr ession. In this study we isolated a full-length HFH-3 cDNA clone from a human kidney library which encoded a 351-amino acid protein containi ng a centrally located winged helix DNA binding domain. We demonstrate that HFH-3 is a potent transcriptional activator requiring 138 C-term inal residues for activity. We used in situ hybridization to demonstra te that HFH-3 expression is restricted to the epithelium of the renal distal convoluted tubules. We determined the HFH-3 DNA binding consens us sequence by in vitro DNA binding site selection using recombinant H FH-3 protein and used this consensus sequence to identify putative HFH -3 target genes expressed there. These putative HFH-3 target genes inc lude the Na/K-ATPase, Na/H and anion exchangers, E-cadherin, and miner alocorticoid receptor genes as well as genes for the transcription fac tors HNF-1, vHNP-1, and HNF-4.