Jf. Waring et al., THE HUMAN-LEUKOCYTE ANTIGEN A2 INTERFERON-STIMULATED RESPONSE ELEMENTCONSENSUS SEQUENCE BINDS A NUCLEAR FACTOR REQUIRED FOR CONSTITUTIVE EXPRESSION, The Journal of biological chemistry, 270(20), 1995, pp. 12276-12285
Both constitutive and interferon-inducible enhancer-like elements have
been identified previously in the promoter of human leukocyte antigen
(HLA) class I genes. One of these sites is termed the interferon-stim
ulated response element (ISRE). We have tested the function of an ISRE
consensus sequence in the human HLA class I gene HLA-A2 and confirmed
previous studies that showed that the HLA-A2 ISRE consensus sequence
does not mediate a response to interferons. However, deletion of the I
SRE consensus sequence caused a severalfold reduction in the constitut
ive expression of the HLA-A2 gene in K562 and Jurkat cells. Mobility s
hift assays performed with the HLA-A2 ISRE revealed the presence of a
constitutive binding protein (ISRE/CBP). This protein binds specifical
ly to the HLA-A2 ISRE sequence, and binding is not efficiently compete
d by the ISRE sequences of the HLA-B7 or ISG54 genes. Substitution of
the HLA-B7 or ISG54 ISRE sequences for the HLA-A2 ISRE sequence caused
a severalfold reduction in the constitutive expression of the HLA-A2
gene. Mass determinations showed the ISRE/CBP to be 105 kDa, different
than any previously characterized ISRE binding proteins. We propose t
hat ISRE/CBP is a novel positive transcriptional regulatory factor for
the HLA-A2 gene that may contribute to the differential expression of
HLA-A versus HLA-B genes.