Blood, Vol. 92 No. 7 (October 1), 1998:
pp. 2399-2409
Distinct Regulatory Mechanisms for Interferon-
/
(IFN-/)- and IFN-
-Mediated Induction of Ly-6E Gene in B
Cells
Mehran M. Khodadoust,
Khuda Dad Khan,
Eun-ha Park, and
Alfred L.M. Bothwell
From the Section of Immunobiology, Yale University School of
Medicine, New Haven, CT; and the Department of Medicine, Division of
Hematology and Oncology, Duke University Medical Center, Durham, NC.
The murine Ly6-E gene is transcriptionally induced by
interferon-
/
(IFN-/) and IFN-
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-/-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-/-mediated induction of the Ly6-E gene. These results show the complexity involved in achieving cell-type specificity in IFN-mediated gene regulation.
