Isolation and characterization of a third isoform of human hepatocyte nuclear factor 4

Gene. 1996 Sep 16;173(2):275-80. doi: 10.1016/0378-1119(96)00183-7.


Hepatocyte nuclear factor 4 (HNF-4) is an essential positive regulator of a large number of liver-specific genes. We report here the isolation of three HNF-4 isoforms from a human liver cDNA library. hHNF-4A and hHNF-4B, differing by the insertion of 10 amino acids in the C-terminal region, have been previously identified in mouse, rat and human liver. The novel isoform, hHNF-4C, is identical to hHNF-4A and B in the regions encompassing the DNA-binding and dimerization domains, but contains a different C-terminal domain. Similar to the other isoforms, hHNF-4C is produced in a limited number of tissues and represents 2.6-13% of the total hHNF-4 mRNA population, depending on the cell type. The chromosomal origin of all three isoforms has been localized to human chromosome 20. hHNF-4C can form heterodimers with hHNF-4A and B in vitro, and exhibits similar transactivation potential as hHNF-4A or B in transient transfection assays, suggesting that the divergent C-terminal region is not part of the transactivation domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cell Line
  • Chromosome Mapping
  • Chromosomes, Human, Pair 20
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Gene Expression
  • Hepatocyte Nuclear Factor 4
  • Humans
  • Liver / metabolism*
  • Molecular Conformation
  • Molecular Sequence Data
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / isolation & purification*
  • Phosphoproteins / metabolism
  • Protein Binding
  • Rats
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / isolation & purification*
  • Transcription Factors / metabolism
  • Transcriptional Activation


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Hepatocyte Nuclear Factor 4
  • MLX protein, human
  • Phosphoproteins
  • Tcfl4 protein, mouse
  • Transcription Factors
  • DNA

Associated data

  • GENBANK/X87870
  • GENBANK/X87871
  • GENBANK/X87872