Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes

A. Weisz, P. Marx, R. Sharf, E. Appella, P. H. Driggers, K. Ozato, B. Z. Levi

Research output: Contribution to journalArticle

Abstract

The promoter regions of many interferon-inducible genes share a short DNA sequence motif, termed the interferon consensus sequence (ICS) to which several regulatory proteins bind. A murine cDNA which encodes an ICS binding protein has been reported (M-ICSBP). The cloning of the human homologue of ICSBP (H-ICSBP) is described. H-ICSBP shares high sequence homology with its murine cognate. The derived sequence of H-ICSBP reveals restricted homology within the first 120 amino acids to three other interferon regulatory factors, IRF-1, IRF-2, and ISGF3γ. Truncated ICSBP lacking the first 33 amino-terminal amino acids fails to bind to the ICS, indicating that at least part of the DNA binding domain is located within the well conserved amino terminus. H-ICSBP is expressed exclusively in cell lines of hematopoietic origin. The results of transient transfection assays carried out either in hematopoietic or nonhematopoietic cells suggest that ICSBP acts as a negative regulatory factor on ICS-containing promoters. Furthermore, either interferon-γ (IFN-γ) or IFN-β can alleviate the repression mediated by ICSBP. Therefore, ICSBP may be involved in maintaining submaximal transcriptional activity of IFN-inducible genes in hematopoietic cells. IFN treatment would then alleviate repression allowing maximal transcriptional activity of these genes.

Original languageEnglish (US)
Pages (from-to)25589-25596
Number of pages8
JournalJournal of Biological Chemistry
Volume267
Issue number35
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Weisz, A., Marx, P., Sharf, R., Appella, E., Driggers, P. H., Ozato, K., & Levi, B. Z. (1992). Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes. Journal of Biological Chemistry, 267(35), 25589-25596.