Independent regulation of HNF-1 alpha and HNF-1 beta by retinoic acid in F9 teratocarcinoma cells

EMBO J. 1991 Aug;10(8):2231-6. doi: 10.1002/j.1460-2075.1991.tb07759.x.


Hepatocyte Nuclear Factor-1 alpha (HNF-1 alpha) and HNF-1 beta are homeodomain-containing transcription factors which interact with the GTTAATNATTAAC motif essential to the function of more than 15 promoters selectively expressed in the liver. These homeoproteins can form homo- and heterodimers in solution and share identical DNA-binding domains but have different transcriptional activation properties. During retinoic acid (RA) induced differentiation of F9 embryonal carcinoma (EC) cells, which stimulates aspects of pre-implantation embryogenesis, both HNF-1 beta mRNA and immunoreactive DNA-binding activity are strongly induced approximately 24 h post RA-treatment. In contrast, HNF-1 alpha mRNA increases approximately 4-fold after 5 days, concomitant with elevation of HNF-1 alpha DNA-binding activity and expression of the HNF-1 target gene alpha-fetoprotein. These results indicate that HNF-1 alpha and -1 beta expression can be controlled by regulatory hierarchies downstream of primary RA-response genes, and suggest that independent regulatory mechanisms for these factors can confer distinct and interactive developmental functions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • DNA / genetics
  • DNA / metabolism
  • DNA Fingerprinting
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Embryonal Carcinoma Stem Cells
  • Gene Expression Regulation
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta
  • Molecular Sequence Data
  • Neoplastic Stem Cells / metabolism*
  • Nuclear Proteins*
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta
  • DNA