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) 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.
Overdier
D G
DG
Department of Biochemistry, University of Illinois, Chicago, Illinois 60612-7334, USA.
Ye
H
H
Peterson
R S
RS
Clevidence
D E
DE
Costa
R H
RH
D000375:Aging / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000302:isolation & purification; D004268:DNA-Binding Proteins; D004848:Epithelium / Q000737:chemistry; D051858:Forkhead Transcription Factors; D015723:Gene Library; D006801:Humans; D017403:In Situ Hybridization; D007686:Kidney Tubules, Distal / Q000737:chemistry* / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C477894:FOXI1 protein, human; C106349:FOXJ1 protein, human; D051858:Forkhead Transcription Factors; D011994:Recombinant Proteins; D015534:Trans-Activators; D004247:DNA