title: Downregulation of HLA class I gene transcription in choriocarcinoma cells is controlled by the proximal promoter element and can be reversed by CIITA.
abstract: The expression pattern of MHC class I genes in trophoblast cells at the feto-maternal interface is thought to be the basis of the maintenance of pregnancy by protecting the fetus from maternal immune rejection. Transcription of classical HLA class I genes is low or undetectable in most trophoblast cells as well as in JEG-3 and BeWo trophoblast-derived choriocarcinoma cells. The aim of this study was to characterize the regulatory mechanisms that repress HLA-A transcription in these cell types. We show that the -335 to ATG region of the HLA-A11 gene promoter is inactive in JEG-3 and BeWo cells while able to control efficient reporter gene transcription in other cell types, indicating that this region is the target for downregulation of HLA-A expression in choriocarcinoma cell lines. The regulatory sequence involved in HLA-A gene repression was further mapped to a proximal regulatory element within the -107 to +2 ATG region of the promoter. We show that the HLA-A promoter activity cannot be induced by interferon-gamma (IFN-gamma) and that exogenous MHC class II transactivator CIITA is able to induce HLA class I promoter activity in these cells. Stringent transcriptional regulatory mechanisms, implicating the lack of basal and IFN-gamma-inducible class I promoter activity, are thus involved in the downregulation of HLA-A expression in JEG-3 and BeWo trophoblast-derived choriocarcinoma cells.
mesh_terms: D002460:Cell Line; D002822:Choriocarcinoma / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005805:Genes, MHC Class I / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics; D006801:Humans; D009687:Nuclear Proteins; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014327:Trophoblasts / Q000378:metabolism; D014407:Tumor Cells, Cultured