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/DOß Heterodimer1
Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599
Class II transcriptional activator (CIITA) is a master regulator of
MHC class II genes, including DR, DP, and DQ, and MHC class
II-associated genes DM and invariant chain. To determine the repertoire
of genes that is regulated by CIITA and to identify uncharacterized
CIITA-inducible genes, we used representational difference analysis.
Representational difference analysis screens for differentially
expressed transcripts. All CIITA-induced genes were MHC class II
related. We have identified the 
subunit, DN, of the class II
processing factor DO as an additional CIITA-inducible gene. Northern
analysis confirmed that DN is induced by IFN-
in 2fTGH
fibrosarcoma cells, and CIITA is necessary for high-level expression in
B cells. The ß subunit, DOß, is not inducible in fibrosarcoma cells
by IFN- or exogenous CIITA expression. Moreover, in contrast to
other class II genes, DOß expression remains high in the absence of
CIITA in B cells. The promoters for DN and DOß contain the highly
conserved WXY motifs, and, like other class II genes, expression of
both DN and DOß requires RFX. These findings demonstrate that both
DN and DOß are regulated by RFX. However, DN is defined for the
first time as a CIITA-inducible gene, and DOß as a MHC class II gene
whose expression is independent of CIITA.
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