The cystic fibrosis gene has a "housekeeping"-type promoter and is expressed at low levels in cells of epithelial origin. Academic Article uri icon

Overview

MeSH

  • Base Sequence
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Epithelium
  • Humans
  • In Vitro Techniques
  • Molecular Sequence Data
  • Oligonucleotides
  • Tetradecanoylphorbol Acetate
  • Transcription, Genetic

MeSH Major

  • Bronchi
  • Gene Expression Regulation
  • Membrane Proteins
  • Promoter Regions, Genetic
  • Regulatory Sequences, Nucleic Acid

abstract

  • Evaluation of the expression of the cystic fibrosis (CF) gene in human epithelial cell lines demonstrated active, but low level, transcription of the gene. Analysis of 3.8 kilobases of genomic sequences 5' to exon 1 of the CF gene demonstrated no TATA promoter element, but a high G + C content, multiple transcription start sites, and several potential Sp1 binding sites. Fragments of 5'-flanking sequences from 2.2 kilobases to as small as 102 base pairs 5' to the major transcription start site supported constitutive reporter gene expression in epithelial cells, but at low levels, and independent of the length of the 5' fragment. CF gene transcription was down-regulated by phorbol myristate acetate. Importantly, evaluation of freshly isolated normal human bronchial cells also demonstrated CF gene transcription at a relatively low rate. Together, these observations suggest that although the normal CF gene promoter has characteristics of a "housekeeping"-type gene, and the gene is expressed at low levels in cells of organs that manifest the clinical disorder "cystic fibrosis," its expression can be modulated transcriptionally, implying a possible therapeutic approach for the disease.

publication date

  • May 15, 1991

has subject area

  • Base Sequence
  • Bronchi
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Epithelium
  • Gene Expression Regulation
  • Humans
  • In Vitro Techniques
  • Membrane Proteins
  • Molecular Sequence Data
  • Oligonucleotides
  • Promoter Regions, Genetic
  • Regulatory Sequences, Nucleic Acid
  • Tetradecanoylphorbol Acetate
  • Transcription, Genetic

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 1709163

Additional Document Info

start page

  • 9140

end page

  • 9144

volume

  • 266

number

  • 14