HNF-3A, a hepatocyte-enriched transcription factor of novel structure is regulated transcriptionally.
Hepatocyte-specific gene expression requires the interaction of many proteins with multiple binding sites in the regulatory regions. HNF-3 is a site found to be important in the maximal hepatocyte-specific expression of several genes. We find that liver nuclear extracts contain three major binding activities for this site, which we call HNF-3A, HNF-3B, and HNF-3C. Purification from rat liver nuclear extracts of HNF-3A and HNF-3C reveals that each activity corresponds to a distinct polypeptide, as determined by SDS-PAGE. Peptide sequence derived from the most abundant species, HNF-3A, was used for synthesizing probes with which to isolate a cDNA clone of this protein. The encoded protein contains 466 amino acids (48.7 kD) and has binding properties identical to those of the purified protein. A 160-amino-acid region that does not resemble the binding domain of any known transcription factor is essential for DNA binding. The mRNA for HNF-3A is present in the rat liver but not in brain, kidney, intestine, or spleen, and the basis for this difference is cell-specific regulation of HNF-3A gene transcription.
Lai
E
E
Laboratory of Molecular Cell Biology, Rockefeller University, New York, New York 10021.
Prezioso
V R
VR
Smith
E
E
Litvin
O
O
Costa
R H
RH
Darnell
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D051541:Hepatocyte Nuclear Factor 3-alpha; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D051381:Rats; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C496501:Foxa1 protein, rat; D051541:Hepatocyte Nuclear Factor 3-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D004247:DNA