The regulation of HLA class I expression: is HLA-G the odd one out?
The expression of HLA-G in extravillous cytotrophoblast cells coincides with a general lack of classical MHC class I expression in this tissue. This differential expression of HLA-G and classical HLA class I molecules in trophoblasts suggests a tight transcriptional control. Transactivation of classical MHC class I genes is mediated by two groups of juxtaposed cis -acting elements which can be viewed as regulatory modules. The most up-stream module consists of the enhancer A and ISRE, and mediates the constitutive and cytokine-induced expression. The recently identified S-X-Y module is important in the constitutive and CIITA mediated transactivation. Both modules are divergent in HLA-G rendering this gene unresponsive to NF-kappaB, IRF-1, and CIITA mediated induction pathways. However, other known regulatory sequences that could contribute to the tissue-specific expression of HLA-G have so far not been identified in the proximal promoter region (-1500 bp) and in the first five intronic sequences. This implies a unique regulation of HLA-G transcription. Here, the transcriptional control of HLA-G and classical class I molecules in trophoblast cells are discussed.
Gobin
S J
SJ
Department of Immunohematology and Blood Bank, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.
van den Elsen
P J
PJ
D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007108:Immune Tolerance; D008431:Maternal-Fetal Exchange / Q000276:immunology; D011247:Pregnancy; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D014157:Transcription Factors