Distinct Regulatory Mechanisms for Interferon-α/β (IFN-α/β)– and IFN-γ–Mediated Induction of Ly-6E Gene in B Cells

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 transcripition–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.