Repression of virus-induced interferon A promoters by homeodomain transcription factor Ptx1

Mol Cell Biol. 2000 Oct;20(20):7527-40. doi: 10.1128/MCB.20.20.7527-7540.2000.

Abstract

Interferon A (IFN-A) genes are differentially expressed after virus induction. The differential expression of individual IFN-A genes is modulated by substitutions in the proximal positive virus responsive element A (VRE-A) of their promoters and by the presence or absence of a distal negative regulatory element (DNRE). The functional feature of the DNRE is to specifically act by repression of VRE-A activity. With the use of the yeast one-hybrid system, we describe here the identification of a specific DNRE-binding protein, the pituitary homeobox 1 (Ptx1 or Pitx1). Ptx1 is detectable in different cell types that differentially express IFN-A genes, and the endogenous Ptx1 protein binds specifically to the DNRE. Upon virus induction, Ptx1 negatively regulates the transcription of DNRE-containing IFN-A promoters, and the C-terminal region, as well as the homeodomain of the Ptx1 protein, is required for this repression. After virus induction, the expression of the Ptx1 antisense RNA leads to a significant increase of endogenous IFN-A gene transcription and is able to modify the pattern of differential expression of individual IFN-A genes. These studies suggest that Ptx1 contributes to the differential transcriptional strength of the promoters of different IFN-A genes and that these genes may provide new targets for transcriptional regulation by a homeodomain transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • DNA / genetics
  • DNA / metabolism
  • DNA Probes
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Silencing*
  • Genes, Reporter
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Interferon Type I / genetics*
  • Mice
  • Newcastle disease virus / physiology
  • Paired Box Transcription Factors
  • Promoter Regions, Genetic / genetics*
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Response Elements / genetics
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • DNA Probes
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Interferon Type I
  • Paired Box Transcription Factors
  • RNA, Antisense
  • Repressor Proteins
  • Transcription Factors
  • homeobox protein PITX1
  • DNA