Identification of a novel sequence element in the common promoter region of human collagen type IV genes, involved in the regulation of divergent transcription

G Fischer, Cornelia Schmidt, J Opitz, Z Cully, K Kühn, E Pöschl

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

The expression of the heterotrimeric collagen IV molecule alpha 1(IV)2 alpha 2(IV) is essential for the structural integrity and functional properties of all basement membranes. The two genes COL4A1 and COL4A2 that code for the subunits are found closely linked on chromosome 13 in a head-to-head arrangement and are transcribed in divergent directions. We have identified a novel trans-acting factor that binds in vitro to a unique homopyrimidine/homopurine stretch within the shared promoter region of the two collagen IV genes. Additional binding sites have been identified within the first introns of both genes and the consensus sequence CCCTYCCCC for efficient binding has been deduced; the factor was named therefore 'CTC-binding factor' or 'CTCBF'. Mutations in the binding site of CTC-binding factor within the promoter inhibited binding in vitro and resulted in reduced transcription from both genes. The effect of mutations on the transcription of COL4A2 is more pronounced than on the transcription of COL4A1. CTC-binding factor is a nuclear factor that binds dominantly in vitro to the collagen IV promoter and is involved in regulating the expression of both collagen IV genes.

Original languageEnglish
Pages (from-to)687-695
Number of pages9
JournalBiochemical Journal
Volume292
Issue number3
DOIs
Publication statusPublished - 15 Jun 1993

Keywords

  • Base Sequence
  • Binding Sites
  • Binding, Competitive
  • Carrier Proteins
  • Collagen
  • DNA-Binding Proteins
  • Gene Expression Regulation
  • Humans
  • Kinetics
  • Methylation
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • Promoter Regions, Genetic
  • Repressor Proteins
  • Restriction Mapping
  • Trans-Activators
  • Transcription, Genetic

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