Methylation of class II trans-activator promoter IV: a novel mechanism of MHC class II gene control.

TitleMethylation of class II trans-activator promoter IV: a novel mechanism of MHC class II gene control.
Publication TypeJournal Article
Year of Publication2000
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume164
Issue8
Pagination4143-9
Date Published2000
ISSN0022-1767
Abstract

Inhibition of class II trans-activator (CIITA) expression prevents embryonic trophoblast cells from up-regulating MHC class II genes in response to IFN-gamma. 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-gamma-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-gamma-inducible transcription. The inhibition of CpG methylation in Jar cells by treatment with 5-aza-2'-deoxycytidine restores IFN-gamma inducibility to CIITA. This is the first description of an epigenetic mechanism involved in regulation of CIITA and MHC class II gene expression.

URLhttp://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10754309
Short TitleJ Immunol
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