Transcriptional control of MHC genes in fetal trophoblast cells.
Tight control of MHC expression is essential for the outcome of a successful pregnancy. The lack of MHC class II and class I mediated antigen presentation by fetal trophoblast cells is an important mechanism to evade maternal immune recognition. Interestingly, the deficient expression of MHC class II molecules (HLA-DR, -DQ and -DP) and of the classical MHC class I molecules HLA-A and HLA-B is also noted after IFN-gamma treatment in trophoblast-derived cell lines. Our studies show that in trophoblast cell lines the IFN-gamma induced transactivation of HLA-A and HLA-B promoters is repressed. Furthermore, it was found that trophoblast cells lacked IFN-gamma mediated induction of the class II transactivator (CIITA). This lack of CIITA expression in trophoblast cells is due to CIITA promoter hypermethylation. In addition to lack of CIITA expression, trophoblast cells also displayed a repressed expression of RFX5. Together, these observations reveal a silencing of multiple activation pathways that are critical to the transcriptional control of MHC class II and class I antigen presentation functions by trophoblast cells.
van den Elsen
P J
PJ
Division of Molecular Biology, Department of Immunohematology and Blood Transfusion, Building 1, E3-Q, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. pvdelsen@euronet.nl
Gobin
S J
SJ
van der Stoep
N
N
Datema
G
G
Viëtor
H E
HE
D002460:Cell Line; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; C093524:RFX5 protein, human; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators; D007371:Interferon-gamma