title: The role of methylation, DNA polymorphisms and microRNAs on HLA-G expression in human embryonic stem cells.
abstract: The human leukocyte antigen (HLA)-G gene seems to play a pivotal role in maternal tolerance to the fetus. Little is known about HLA-G expression and its molecular control during in vivo human embryogenesis. Human embryonic stem cells (hESC) provide an interesting in vitro model to study early human development. Different studies reported discrepant findings on whether HLA-G mRNA and protein are present or absent in hESC. Several lines of evidence indicate that promoter CpG methylation and 3' untranslated region (3'UTR) polymorphisms may influence HLA-G expression. We investigated how HLA-G expression is linked to the patterns of promoter methylation and explored the role of the 3'UTR polymorphic sites and their binding microRNAs on the post-transcriptional regulation of HLA-G in eight hESC lines. We showed that, while the gross expression levels of HLA-G are controlled by promoter methylation, the genetic constitution of the HLA-G 3'UTR, more specifically the 14bp insertion in combination with the +3187A/A and +3142G/G SNP, plays a major role in HLA-G mRNA regulation in hESC. Our findings provide a solid first step towards future work using hESC as tools for the study of early human developmental processes in normal and pregnancy-related disorders such as preeclampsia.
authors.affiliation: Department of Hematology, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium; Research Group Reproductive Immunology and Implantation (REIM), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium. Electronic address: an.verloes@vub.ac.be.
authors.forename: A
authors.initials: A
authors.lastname: Verloes
authors.affiliation: Research Group Reproduction and Genetics (REGE), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Spits
authors.affiliation: Department of Hematology, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium; Research Group Reproductive Immunology and Implantation (REIM), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Vercammen
authors.affiliation: Research Group Reproduction and Genetics (REGE), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Geens
authors.affiliation: Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, 75475 Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: LeMaoult
authors.affiliation: Research Group Reproduction and Genetics (REGE), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Sermon
authors.affiliation: Department of Quality of Medical Laboratories, Scientific Institute of Public Health, 1050 Brussels, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Coucke
authors.affiliation: Research Group Reproductive Immunology and Implantation (REIM), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium; Research Group Reproduction and Genetics (REGE), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium; Center for Reproductive Medicine, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Van de Velde
mesh_terms: D020413:3' Untranslated Regions; D000483:Alleles; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005787:Gene Frequency; D005838:Genotype; D059951:HLA-G Antigens / Q000235:genetics / Q000378:metabolism*; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens; D035683:MicroRNAs; D020033:Protein Isoforms; D012333:RNA, Messenger; D004247:DNA
keywords: 3′UTR; HLA-G; MicroRNA; Promoter methylation; hESC