HNF-3A, a hepatocyte-enriched transcription factor of novel structure is regulated transcriptionally

• Published in: Genes & development Vol. 4; no. 8; pp. 1427 - 1436
• Main Authors: LAI, E, PREZIOSO, V. R, SMITH, E, LITVIN, O, COSTA, R. H, DARNELL, J. E
• Format: Journal Article
• Language: English
• Published: Cold Spring Harbor, NY Cold Spring Harbor Laboratory 01.08.1990
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Binding Sites; Biological and medical sciences; Cloning, Molecular; DNA - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Electrophoresis, Polyacrylamide Gel; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; genes; Genes. Genome; Hepatocyte Nuclear Factor 3-alpha; liver; Liver - cytology; Liver - metabolism; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Nuclear Proteins; Rats; transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Rat; Nucleotide sequence; Transcription; Liver; Rodentia; Footprinting technique; Tissue specificity; Molecular interaction; Gel retardation technique; Northern blotting; Vertebrata; Regulation(control); Mammalia; Complementary DNA; Gene; Hepatocyte; DNA; Molecular cloning; Aminoacid sequence
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.4.8.1427

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.