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J Biol Chem, Vol. 273, Issue 52, 34775-34783, December 25, 1998
From the Departments of Nuclear factor of activated T cells (NFAT) plays
an important role in expression of many cytokine genes including
interleukin-2 and interleukin-4. However, its role in interferon-
The Roles of Nuclear Factor of Activated T Cells and Ying-Yang
1 in Activation-induced Expression of the Interferon-
Promoter in T Cells
,,, and
Pediatrics and
Immunology, University of Washington,
Seattle, Washington 98195, and ¶ Tularik, Inc.,
South San Francisco, California 94080
(IFN-) expression is not well understood. In the current studies,
two strong NFAT-binding sites in the IFN- promoter were identified
by DNase I footprint analysis at positions 
280 to 270 and 163 to
155. NFATp bound independently to both sites and was required for the
formation of a composite element with AP-1 spanning position 163 to
147. In Jurkat T cells and primary lymphocytes, activation-induced expression of IFN- reporter constructs containing point mutations in
either NFAT site or the AP-1 component of the composite site was
decreased by ~40-65%. Despite elimination of both strong
NFAT-binding sites, the IFN- promoter remained completely sensitive
to inhibition by cyclosporin. This suggests that other elements in the
IFN- promoter, such as the IFN- proximal element, are sufficient
for cyclosporin sensitivity of this gene. Ying-Yang 1 (YY1), a
potential inhibitor of IFN- expression, binds to sites located
between the two NFAT sites. Mutation of the YY1 sites alone had little effect on IFN- promoter activity. However, mutation of both the NFAT
and YY1-binding sites abolished activation-induced expression in
primary murine splenocytes but not in Jurkat T cells. This suggests
that under some conditions, YY1 may play a positive role in
activation-induced transcription of IFN-.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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