Silencer activity in the interferon-A gene promoters

J Biol Chem. 1997 Sep 5;272(36):22788-99. doi: 10.1074/jbc.272.36.22788.

Abstract

Interferon-A (IFN-A) differential gene expression is modulated by a complex interplay between cis-acting DNA elements and the corresponding specific trans-regulating factors. Substitutions in the proximal virus-responsive element of the interferon-A (IFN-A) promoters contribute to their differential gene expression. The 5' distal silencing region in the weakly virus-inducible murine IFN-A11 gene has been previously delimited. DNase I footprinting experiments and transient gene expression assays demonstrate identical silencing activity in equivalent regions of the genes for IFN-A11 and IFN-A4 promoters. A minimal 20-mer distal negative regulatory element (DNRE) in both promoters is necessary and sufficient for the silencing and a region in the highly inducible IFN-A4 promoter located between the silencer and the virus-responsive element overrides the silencer activity. Mutations in the central region of the DNRE, causing derepression, also altered the formation of one of the two major DNA-protein complexes. One of these contains a protein related to or identical to the high mobility group I(Y) proteins, while the other complex contains a major protein present in uninduced and virus-induced cells with a molecular mass of 38 kDa, which may be related to the silencer activity. Similar DNREs are present in other virus-uninducible IFN-A promoters, and these data suggest that a common silencer may mediate the transcriptional repression in different genes of this family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cell Nucleus / metabolism
  • DNA
  • DNA Footprinting
  • HeLa Cells
  • High Mobility Group Proteins / metabolism
  • Humans
  • Interferon-alpha / genetics*
  • Interferon-alpha / metabolism
  • Molecular Sequence Data
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic*
  • Protein Binding
  • Regulatory Sequences, Nucleic Acid
  • Transcription, Genetic*
  • Transfection

Substances

  • High Mobility Group Proteins
  • Interferon-alpha
  • Nuclear Proteins
  • DNA
  • NAD(P)H Dehydrogenase (Quinone)