An interferon-γ activation sequence mediates the transcriptional regulation of the IgG Fc receptor type IC gene by interferon-γ

Ronald L. Paquette, M. Ruby minosa, Mithelesh C. Verma, Stephen D. Nimer, H. Phillip Koeffler

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Expression of the IgG Fc receptor type I (FcγRI) on myeloid cells is dramatically increased by treatment with interferon-γ (IFN-γ). We observed that FcγRI transcript levels in monoblast-like U937 cells were elevated within 3 hr and peaked 12 hr after exposure to IFN-γ. Treatment of U937 with IFN-γ for 9 hr in the presence of cycloheximide led to super-induction of FcγRI expression. Nuclear run-on analysis revealed that the rate of FcγRI transcription was increased by IFN-γ. Genomic sequence upstream of the FcγRIC gene was cloned and subjected to primer extension analysis, which demonstrated a single transcription initiation site without a TATA box. Transient transfections of CAT reporter gene constructs containing various FcγRIC promoter sequences into U937 cells revealed that a 20-bp region surrounding the transcription start site (-7 to +13) was capable of mediating transcription initiation and that an IFN-γ responsive element (GIRE) was present within 74 bp upstream of the transcription initiation site. A 17-bp sequence between positions -51 and -35 conferred IFN-γ responsiveness on a heterologous promoter. Double-stranded GIRE sequence, but not a scrambled sequence, was specifically bound by nuclear proteins from IFN-γ treated U937 cells. Gel shift experiments further showed that the STAT1α protein bound to the FcγRIC GIRE in response to IFN-γ treatment of U937 cells. The FcγRIC GIRE is homologous to the IFN-γ activation sequence (GAS) of the guanylate binding protein and to X box elements of class II MHC genes. Our results demonstrate that transcriptional regulation of the FcγRIC gene by IFN-γ involves the binding of STAT1α to a 17-bp GAS homology in the proximal promoter.

Original languageEnglish (US)
Pages (from-to)841-851
Number of pages11
JournalMolecular Immunology
Volume32
Issue number12
DOIs
StatePublished - Aug 1995
Externally publishedYes

Keywords

  • Fc receptor
  • interferon-γ
  • STAT protein
  • transcriptional regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

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