title: Methylation and transcripts expression at the imprinted GNAS locus in human embryonic and induced pluripotent stem cells and their derivatives.
abstract: Data from the literature indicate that genomic imprint marks are disturbed in human pluripotent stem cells (PSCs). GNAS is an imprinted locus that produces one biallelic (Gsα) and four monoallelic (NESP55, GNAS-AS1, XLsα, and A/B) transcripts due to differential methylation of their promoters (DMR). To document imprinting at the GNAS locus in PSCs, we studied GNAS locus DMR methylation and transcript (NESP55, XLsα, and A/B) expression in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) derived from two human fibroblasts and their progenies. Results showed that (1) methylation at the GNAS locus DMRs is DMR and cell line specific, (2) changes in allelic transcript expression can be independent of a change in allele-specific DNA methylation, and (3) interestingly, methylation at A/B DMR is correlated with A/B transcript expression. These results indicate that these models are valuable to study the mechanisms controlling GNAS methylation, factors involved in transcript expression, and possibly mechanisms involved in the pathophysiology of pseudohypoparathyroidism type 1B.
authors.affiliation: INSERM U986, Hôpital Bicêtre, Le Kremlin Bicêtre 94276, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Grybek
authors.affiliation: UEVE UMR 861, I-Stem, AFM, Evry 91030, France; INSERM UMR 861, I-Stem, AFM, Evry 91030, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Aubry
authors.affiliation: INSERM U986, Hôpital Bicêtre, Le Kremlin Bicêtre 94276, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Maupetit-Méhouas
authors.affiliation: INSERM U986, Hôpital Bicêtre, Le Kremlin Bicêtre 94276, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Stunff
authors.affiliation: CECS, I-Stem, AFM, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, Evry 91030, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Denis
authors.affiliation: CECS, I-Stem, AFM, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, Evry 91030, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Girard
authors.affiliation: INSERM U986, Hôpital Bicêtre, Le Kremlin Bicêtre 94276, France; Service d'Endocrinologie Pédiatrique, Hôpital Bicêtre-AP-HP, Le Kremlin Bicêtre 94276, France; Centre de Référence des Maladies Rares du Métabolisme Phospho-Calcique Hôpital Bicêtre, Le Kremlin Bicêtre 94276, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Linglart
authors.affiliation: INSERM U986, Hôpital Bicêtre, Le Kremlin Bicêtre 94276, France; Centre de Référence des Maladies Rares du Métabolisme Phospho-Calcique Hôpital Bicêtre, Le Kremlin Bicêtre 94276, France; Laboratoire de Biochimie Hormonale et Génétique, Hôpital Bichat Claude Bernard-AP-HP, Paris 75018, France. Electronic address: caroline.silve@inserm.fr.
authors.forename: Caroline
authors.initials: C
authors.lastname: Silve
mesh_terms: D000483:Alleles; D002460:Cell Line; D002864:Chromogranins; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D056426:Genetic Loci; D018392:Genomic Imprinting; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs