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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)
David G.
Overdier
,
Honggang
Ye
,
Richard S.
Peterson
,
Derek E.
Clevidence
and
Robert H.
Costa
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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Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.
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