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Volume 271, Number 47,
Issue of November 22, 1996
pp. 29813-29821
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
The Locus-specific Enhancer Activity of the Class I Major
Histocompatibility Complex Interferon-responsive Element Is Associated
with a -Interferon (IFN)-inducible Factor Distinct from
STAT1 , p48, and IFN Regulatory Factor-1
(Received for publication, May 20, 1996, and in revised form, July 25, 1996)
Abbe N.
Vallejo
and
Larry R.
Pease
From the Department of Immunology, Mayo Clinic-Foundation,
Rochester, Minnesota 55905
Recent analyses of the upstream regulatory
regions of the class I major histocompatibility complex genes in higher
primates provided a generalized structural basis for the differential
expression of A- and B-locus gene products in
response to specific physiological stimulus. Among the regulatory
sequences that differ between the loci is the interferon-responsive
element (IRE). While the B-IRE is conserved, the
A-IREs have species-specific sequence variation. We
previously demonstrated that the B-IRE was an interferon
(IFN)-inducible enhancer, whereas none of the A-IREs were
functional. In the present study, we examined the biochemical basis for
the enhancer activity of the conserved B-IRE and found that
this may be attributed to a novel -IFN-inducible factor. This factor
accumulated in nuclei of cells within minutes of exposure to -IFN.
Its appearance was independent of de novo protein
synthesis. However, it was not detected in nuclei of cells treated with
herbimycin A, suggesting that its appearance depends on a protein
kinase activation pathway. Supershift assays indicated that it was
distinct from STAT1 , IFN regulatory factor-1, and p48, transcription
factors known to bind IRE-like sequences found in regulatory regions of
many non-major histocompatibility complex -IFN-responsive genes.
Competition assays show that this novel factor bound B-IRE
with relatively high affinity, about 100-fold more than that for the
A-IRE sequence. This factor was also present in STAT1
and p48 somatic mutants that also exhibited B-IRE enhancer
activity in reporter gene bioassays in a manner similar to those seen
with wild type cells. These observations indicate the existence of a
novel -IFN-dependent transcriptional activation pathway
that correlates with the differential enhancer activity of the
HLA-B IRE.

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Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.
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