PMID- 28131957 OWN - NLM STAT- MEDLINE DCOM- 20171122 LR - 20180329 IS - 1876-7753 (Electronic) IS - 1873-5061 (Linking) VI - 19 DP - 2017 Mar TI - The role of methylation, DNA polymorphisms and microRNAs on HLA-G expression in human embryonic stem cells. PG - 118-127 LID - S1873-5061(17)30005-3 [pii] LID - 10.1016/j.scr.2017.01.005 [doi] AB - 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. CI - Copyright (c) 2017 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Verloes, A AU - Verloes A AD - 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. FAU - Spits, C AU - Spits C AD - Research Group Reproduction and Genetics (REGE), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium. FAU - Vercammen, M AU - Vercammen M AD - 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. FAU - Geens, M AU - Geens M AD - Research Group Reproduction and Genetics (REGE), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium. FAU - LeMaoult, J AU - LeMaoult J AD - Service de Recherches en Hemato-Immunologie, Hopital Saint-Louis, 75475 Paris, France. FAU - Sermon, K AU - Sermon K AD - Research Group Reproduction and Genetics (REGE), Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium. FAU - Coucke, W AU - Coucke W AD - Department of Quality of Medical Laboratories, Scientific Institute of Public Health, 1050 Brussels, Belgium. FAU - Van de Velde, H AU - Van de Velde H AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170109 PL - England TA - Stem Cell Res JT - Stem cell research JID - 101316957 RN - 0 (3' Untranslated Regions) RN - 0 (HLA-G Antigens) RN - 0 (MicroRNAs) RN - 0 (Protein Isoforms) RN - 0 (RNA, Messenger) RN - 9007-49-2 (DNA) SB - IM MH - 3' Untranslated Regions MH - Alleles MH - Cell Line MH - DNA/chemistry/genetics/*metabolism MH - DNA Methylation MH - Gene Frequency MH - Genotype MH - HLA-G Antigens/genetics/*metabolism MH - Human Embryonic Stem Cells/cytology/*metabolism MH - Humans MH - MicroRNAs/genetics/*metabolism MH - Polymorphism, Single Nucleotide MH - Promoter Regions, Genetic MH - Protein Isoforms/genetics/metabolism MH - RNA, Messenger/metabolism MH - Sequence Analysis, DNA OTO - NOTNLM OT - 3'UTR OT - HLA-G OT - MicroRNA OT - Promoter methylation OT - hESC EDAT- 2017/01/31 06:00 MHDA- 2017/11/29 06:00 CRDT- 2017/01/30 06:00 PHST- 2016/06/02 00:00 [received] PHST- 2016/11/29 00:00 [revised] PHST- 2017/01/04 00:00 [accepted] PHST- 2017/01/31 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/01/30 06:00 [entrez] AID - S1873-5061(17)30005-3 [pii] AID - 10.1016/j.scr.2017.01.005 [doi] PST - ppublish SO - Stem Cell Res. 2017 Mar;19:118-127. doi: 10.1016/j.scr.2017.01.005. Epub 2017 Jan 9.