The locus-specific enhancer activity of the class I major histocompatibility complex interferon-responsive element is associated with a γ-interferon (IFN)-inducible factor distinct from STAT1α, p48, and IFN regulatory factor-1

Abbe N. Vallejo, Larry R. Pease

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Recent analyses of the upstream regulatory regions of the class I major histocompatibility complex genes in higher primates provided a generalized structural basis for the differential expression of A- and B-locus gene products in response to specific physiological stimulus. Among the regulatory sequences that differ between the loci is the interferon-responsive element (IRE). While the B-IRE is conserved, the A-IREs have species-specific sequence variation. We previously demonstrated that the B-IRE was an interferon (IFN)-inducible enhancer, whereas none of the A-IREs were functional. In the present study, we examined the biochemical basis for the enhancer activity of the conserved B-IRE and found that this may be attributed to a novel γ-IFN-inducible factor. This factor accumulated in nuclei of cells within minutes of exposure to γ-IFN. Its appearance was independent of de novo protein synthesis. However, it was not detected in nuclei of cells treated with herbimycin A, suggesting that its appearance depends on a protein kinase activation pathway. Supershift assays indicated that it was distinct from STAT1α, IFN regulatory factor-1, and p48, transcription factors known to bind IRE-like sequences found in regulatory regions of many non-major histocompatibility complex γ-IFN-responsive genes. Competition assays show that this novel factor bound B-IRE with relatively high affinity, about 100-fold more than that for the A-IRE sequence. This factor was also present in STAT1α and p48 somatic mutants that also exhibited B-IRE enhancer activity in reporter gene bioassays in a manner similar to those seen with wild type cells. These observations indicate the existence of a novel γ-IFN-dependent transcriptional activation pathway that correlates with the differential enhancer activity of the HLA-B IRE.

Original languageEnglish (US)
Pages (from-to)29813-29821
Number of pages9
JournalJournal of Biological Chemistry
Volume271
Issue number47
DOIs
StatePublished - Nov 30 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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