Two distinct factors interact with the promoter regions of several liver-specific genes

EMBO J. 1988 Jun;7(6):1711-9.

Abstract

A segment of the human alpha 1-antitrypsin (alpha 1AT) 5'-flanking region comprising nucleotides -137 to -37 from the start of transcription is sufficient to drive liver-specific transcription from the homologous alpha 1AT promoter and from the heterologous SV40 promoter. In this paper we characterize two proteins, LF-A1 and LF-B1, whose ability to bind wild-type and mutant alpha 1AT promoter segments correlates with the ability of these segments to activate transcription in vivo. DNase I protection and methylation interference analysis reveals that LF-A1 recognizes sequences present in the regulatory region of the human alpha 1-antitrypsin, apolipoprotein A1 and haptoglobin-related genes. These sequences share a common 5' TGG/A A/C CC 3' motif. LF-B1 binds to the palindrome 5' TGGTTAAT/ATTCACCA 3' which is present in the human alpha 1-antitrypsin gene between positions -78 and -62 from the start of transcription. LF-B1 also recognizes a related sequence present in the human albumin gene between -66 and -50. These results suggest that LF-A1 and LF-B1 are common positive trans-acting factors which are required for the expression of several genes in the hepatocyte.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / genetics
  • Animals
  • Apolipoprotein A-I
  • Apolipoproteins A / genetics
  • Base Sequence
  • Binding Sites
  • Enzyme Induction
  • Gene Expression Regulation*
  • Genes, Viral
  • Haptoglobins / genetics
  • Humans
  • Liver / metabolism*
  • Mice
  • Molecular Sequence Data
  • Organ Specificity
  • Promoter Regions, Genetic*
  • Sequence Homology, Nucleic Acid
  • Simian virus 40 / genetics
  • Transcription Factors / metabolism*
  • alpha 1-Antitrypsin / biosynthesis
  • alpha 1-Antitrypsin / genetics*

Substances

  • Albumins
  • Apolipoprotein A-I
  • Apolipoproteins A
  • Haptoglobins
  • Transcription Factors
  • alpha 1-Antitrypsin