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Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322
Inhibition of class II trans-activator (CIITA)
expression prevents embryonic trophoblast cells from up-regulating MHC
class II genes in response to IFN-
. This is thought to be one
mechanism of maternal tolerance to the fetal allograft. The CIITA gene
is regulated by four distinct promoters; promoter III directs
constitutive (B cell) expression, and promoter IV regulates
IFN-
-inducible expression. Using in vivo genomic footprinting,
promoter-reporter analysis, Southern blot analysis, and RT-PCR, we have
examined the cause of CIITA silencing in a trophoblast-derived cell
line. We report here that methylation of promoter IV DNA at CpG sites
in Jar cells prevents promoter occupancy and IFN-
-inducible
transcription. The inhibition of CpG methylation in Jar cells by
treatment with 5-aza-2'-deoxycytidine restores IFN-
inducibility to
CIITA. This is the first description of an epigenetic mechanism
involved in regulation of CIITA and MHC class II gene
expression.
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