title: Genetic and epigenetic control of the major histocompatibility complex class Ib gene HLA-G in trophoblast cell lines.
abstract: The transcriptional regulation of the major histocompatibility complex class (MHC) Ib gene HLA-G differs from the classical MHC class I genes. The cis-acting regulatory elements typical for classical MHC class I promoters are divergent in the promoter of HLA-G, rendering this gene unresponsive to NF-kappaB, IRF-1, and class II transactivator (CIITA)-mediated activation pathways. However, as we have previously shown, transactivation of HLA-G is regulated by CREB-1. Because CREB-1 is ubiquitously expressed, this observation does not explain the tissue-restricted expression of HLA-G in extravillous cytotrophoblasts. Using HLA-G-expressing JEG-3 cells and HLA-G-deficient JAR trophoblast-derived choriocarcinoma cells as a model, we have investigated the contribution of DNA methylation and histone acetylation in the transcriptional activation of HLA-G. Despite similar levels of DNA methylation both in JEG3 and JAR cells, we found the levels of histone acetylation in HLA-G promoter chromatin to be significantly enhanced in JEG3 cells coinciding with HLA-G expression.
authors.affiliation: Division of Molecular Biology, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tjadine M
authors.initials: TM
authors.lastname: Holling
authors.forename: Marloes W T
authors.initials: MW
authors.lastname: Bergevoet
authors.forename: Rutger J
authors.initials: RJ
authors.lastname: Wierda
authors.forename: Marja C J A
authors.initials: MC
authors.lastname: van Eggermond
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van den Elsen
mesh_terms: D000107:Acetylation; D001483:Base Sequence; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology
chemical_list: D002843:Chromatin; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D006657:Histones