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Volume 272, Number 21, Issue of May 23, 1997 pp. 13725-13730
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

The Winged Helix Transcriptional Activator HFH-3 Is Expressed in the Distal Tubules of Embryonic and Adult Mouse Kidney

(Received for publication, March 7, 1997, and in revised form, March 21, 1997)

From the Department of Biochemistry, University of Illinois, Chicago, Illinois 60612-7334

The hepatocyte nuclear factor-3 (HNF-3)/fork head homolog (HFH) proteins are an extensive family of transcription factors, which share homology in the winged helix DNA binding domain. Members of the HFH/winged helix family have been implicated in cell fate determination during pattern formation, in organogenesis, and in cell-type-specific gene expression. In this study we isolated a full-length HFH-3 cDNA clone from a human kidney library which encoded a 351-amino acid protein containing a centrally located winged helix DNA binding domain. We demonstrate that HFH-3 is a potent transcriptional activator requiring 138 C-terminal residues for activity. We used in situ hybridization to demonstrate that HFH-3 expression is restricted to the epithelium of the renal distal convoluted tubules. We determined the HFH-3 DNA binding consensus sequence by in vitro DNA binding site selection using recombinant HFH-3 protein and used this consensus sequence to identify putative HFH-3 target genes expressed there. These putative HFH-3 target genes include the Na/K-ATPase, Na/H and anion exchangers, E-cadherin, and mineralocorticoid receptor genes as well as genes for the transcription factors HNF-1, vHNF-1, and HNF-4.

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