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

被引:88
作者
Morris, AC [1 ]
Spangler, WE [1 ]
Boss, JM [1 ]
机构
[1] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA
关键词
D O I
10.4049/jimmunol.164.8.4143
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Inhibition of class II trails-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 TV regulates IFN-gamma-inducible expression. Using in Give 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,vith 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.
引用
收藏
页码:4143 / 4149
页数:7
相关论文
共 59 条
[1]   A TRANSFORMING GROWTH-FACTOR-BETA-2 (TGF-BETA-2)-LIKE IMMUNOSUPPRESSIVE FACTOR IN AMNIOTIC-FLUID AND LOCALIZATION OF TGF-BETA-2 MESSENGER-RNA IN THE PREGNANT UTERUS [J].
ALTMAN, DJ ;
SCHNEIDER, SL ;
THOMPSON, DA ;
CHENG, HL ;
TOMASI, TB .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 172 (05) :1391-1401
[2]   HIGH-LEVELS OF DENOVO METHYLATION AND ALTERED CHROMATIN STRUCTURE AT CPG ISLANDS IN CELL-LINES [J].
ANTEQUERA, F ;
BOYES, J ;
BIRD, A .
CELL, 1990, 62 (03) :503-514
[3]   PLACENTAL TISSUE FROM HUMAN MISCARRIAGES EXPRESSES CLASS-II HLA-DR ANTIGENS [J].
ATHANASSAKIS, I ;
AIFANTIS, Y ;
MAKRYGIANNAKIS, A ;
KOUMANTAKIS, E ;
VASSILIADIS, S .
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 1995, 34 (05) :281-287
[4]   INDUCTION OF CLASS-II MHC ANTIGEN EXPRESSION ON THE MURINE PLACENTA BY 5-AZACYTIDINE CORRELATES WITH FETAL ABORTION [J].
ATHANASSAKISVASSILIADIS, I ;
GALANOPOULOS, VK ;
GRIGORIOU, M ;
PAPAMATHEAKIS, J .
CELLULAR IMMUNOLOGY, 1990, 128 (02) :438-449
[5]  
BASTA PV, 1987, J IMMUNOL, V138, P1275
[6]   Regulation of transcription of MHC class II genes [J].
Boss, JM .
CURRENT OPINION IN IMMUNOLOGY, 1997, 9 (01) :107-113
[7]   REGULATION OF A TRANSFECTED HUMAN CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX GENE IN HUMAN-FIBROBLASTS [J].
BOSS, JM ;
STROMINGER, JL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (23) :9139-9143
[8]  
BOURCRAUT J, 1993, IMMUNOGENETICS, V38, P117
[9]   CLASS-II TRANSACTIVATOR (CIITA) IS SUFFICIENT FOR THE INDUCIBLE EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II GENES [J].
CHANG, CH ;
FONTES, JD ;
PETERLIN, M ;
FLAVELL, RA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (04) :1367-1374
[10]   MOLECULAR ANALYSIS OF G1B AND G3A IFN-GAMMA MUTANTS REVEALS THAT DEFECTS IN CIITA OR RFX RESULT IN DEFECTIVE CLASS-II MHC AND II-GENE INDUCTION [J].
CHIN, KC ;
MAO, C ;
SKINNER, C ;
RILEY, JL ;
WRIGHT, KL ;
MORENO, CS ;
STARK, GR ;
BOSS, JM ;
TING, JPY .
IMMUNITY, 1994, 1 (08) :687-697