Distinct regulatory mechanisms for interferon-α/β (IFN-α/β)- and IFN-γ-mediated induction of Ly-6E gene in B cells

Mehran M. Khodadoust, Khuda Dad Khan, Eun Ha Park, Alfred L.M. Bothwell

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The murine Ly6-E gene is transcriptionally induced by interferon-α/β (IFN-α/β) and IFN-γ in a variety of distinct cell types. The mechanism of IFN inducibility in B-cell lines was investigated by deletion analysis of the promoter and by identifying DNA binding proteins in mobility shift assays. A region located in the distal part of the promoter at -2.3 kb contributed to inducibility by both types of IFNs. This region contains a novel element in addition to the previously well-characterized IFN-stimulated response element (ISRE). The probes containing ISRE detected IFN-inducible complexes in mobility shift assays and the signal transducer and activator of transcription-1 was found to be in these complexes from cells treated with either type of IFN. An additional element present in the proximal part of the promoter at position -109 is also required for IFN-α/β-mediated induction. These data suggested a cooperative interaction between these physically disparate regulatory regions. A crucial role for HMGI(Y) protein in this cooperative multiprotein complex is supported by the evidence that inhibition of HMGI(Y) expression via antisense RNA results in the loss of IFN-α/β- mediated induction of the Ly6-E gene. These results show the complexity involved in achieving cell-type specificity in IFN-mediated gene regulation.

Original languageEnglish (US)
Pages (from-to)2399-2409
Number of pages11
JournalBlood
Volume92
Issue number7
DOIs
StatePublished - Oct 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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