TY - JOUR
T1 - Methylation of class II trans-activator promoter IV
T2 - A novel mechanism of MHC class II gene control
AU - Morris, Ann C.
AU - Spangler, Wendi E.
AU - Boss, Jeremy M.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2000/4/15
Y1 - 2000/4/15
N2 - Inhibition of class II trans-activator (CIITA) expression prevents embryonic trophoblast cells from up-regulating MHC class II genes in response to IFN-γ. This is thought to be one mechanism of maternal tolerance to the fetal allograft. The CIITA gene is regulated by four distinct promoters; promoter HI directs constitutive (B cell) expression, and promoter IV regulates IFN-γ-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-γ-inducible transcription. The inhibition of CpG methylation in Jar cells by treatment with 5-aza-2'- deoxycytidine restores IFN-γ inducibility to CIITA. This is the first description of an epigenetic mechanism involved in regulation of CIITA and MHC class II gene expression.
AB - Inhibition of class II trans-activator (CIITA) expression prevents embryonic trophoblast cells from up-regulating MHC class II genes in response to IFN-γ. This is thought to be one mechanism of maternal tolerance to the fetal allograft. The CIITA gene is regulated by four distinct promoters; promoter HI directs constitutive (B cell) expression, and promoter IV regulates IFN-γ-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-γ-inducible transcription. The inhibition of CpG methylation in Jar cells by treatment with 5-aza-2'- deoxycytidine restores IFN-γ 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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U2 - 10.4049/jimmunol.164.8.4143
DO - 10.4049/jimmunol.164.8.4143
M3 - Article
C2 - 10754309
AN - SCOPUS:0034655297
SN - 0022-1767
VL - 164
SP - 4143
EP - 4149
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -