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

J Biol Chem. 1992 Dec 15;267(35):25589-96.

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 ISGF3 gamma. 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-gamma (IFN-gamma) or IFN-beta 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Northern
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / genetics
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Cycloheximide / pharmacology
  • DNA / genetics
  • DNA / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Enhancer Elements, Genetic* / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Library
  • HeLa Cells
  • Humans
  • Interferon Regulatory Factors
  • Interferon-beta / pharmacology*
  • Interferon-gamma / pharmacology*
  • Lung / physiology
  • Molecular Sequence Data
  • Plasmids
  • Promoter Regions, Genetic* / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / metabolism
  • Repressor Proteins*
  • Sequence Homology, Amino Acid
  • Transfection
  • Tumor Cells, Cultured
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Interferon Regulatory Factors
  • RNA, Messenger
  • Recombinant Proteins
  • Repressor Proteins
  • interferon regulatory factor-8
  • Interferon-beta
  • Interferon-gamma
  • DNA
  • Cycloheximide
  • Chloramphenicol O-Acetyltransferase
  • beta-Galactosidase

Associated data

  • GENBANK/D10520
  • GENBANK/D12749
  • GENBANK/D12750
  • GENBANK/D12751
  • GENBANK/D12752
  • GENBANK/D12753
  • GENBANK/L01427
  • GENBANK/L01429
  • GENBANK/L01441
  • GENBANK/M91196