Positive Regulation of connexin32 Transcription by Hepatocyte Nuclear factor-1alpha

Arch Biochem Biophys. 2002 Nov 15;407(2):160-7. doi: 10.1016/s0003-9861(02)00488-5.

Abstract

Connexin32 (Cx32) encodes the predominant gap junction protein expressed by hepatocytes. We investigated the transcriptional control of Cx32 in expressing and nonexpressing rat liver cell lines and hypothesized that a putative hepatocyte nuclear factor-1 (HNF-1) binding site (centered at mp -187) in the liver-active, P1 promoter is essential for transcription of Cx32. HNF-1alpha was expressed by Cx32-expressing rat liver cell lines and bound the promoter at the -187 site, but was not expressed by non-Cx32-expressing hepatic lines. Stable transfection of non-Cx32-expressing WB-F344 rat liver epithelial cells with HNF-1alpha stimulated a transfected Cx32 promoter element (mp -244 to -33), binding of HNF-1alpha to the -187 site, and expression of endogenous Cx32. Site-directed mutagenesis of this HNF-1 binding site abolished HNF-1alpha binding and proximal promoter activity. Hepatic Cx32 expression was also significantly decreased in HNF-1alpha(-/-) mice. These data indicate that HNF-1alpha is a positive regulator of Cx32 expression in hepatic cells.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Connexins / biosynthesis
  • Connexins / genetics*
  • DNA-Binding Proteins*
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Liver / metabolism*
  • Mice
  • Mice, Knockout
  • Nuclear Proteins*
  • Promoter Regions, Genetic
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Inbred F344
  • Response Elements
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcriptional Activation*
  • Transfection

Substances

  • Connexins
  • DNA-Binding Proteins
  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse
  • Hnf1a protein, rat
  • Hnf1b protein, mouse
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • connexin 32
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta