title: Persistent organic pollutants alter DNA methylation during human adipocyte differentiation.
abstract: Ubiquitous persistent organic pollutants (POPs) can accumulate in humans where they might influence differentiation of adipocytes. The aim of this study was to investigate whether DNA methylation is one of the underlying mechanisms by which POPs affect adipocyte differentiation, and to what extent DNA methylation can be related to gene transcription. Adipocyte differentiation was induced in two human cell models with continuous exposure to different POPs throughout differentiation. From the seven tested POPs, perfluorooctanesulfonic acid (PFOS) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreased lipid accumulation, while tributyltin (TBT) increased lipid accumulation. In human mesenchymal stem cells (hMSCs), TCDD and TBT induced opposite gene expression profiles, whereas after PFOS exposure gene expression remained relatively stable. Genome-wide DNA methylation analysis showed that all three POPs affected DNA methylation patterns in adipogenic and other genes, possibly related to the phenotypic outcome, but without concomitant gene expression changes. Differential methylation was predominantly detected in intergenic regions, where the biological relevance of alterations in DNA methylation is unclear. This study demonstrates that POPs, at environmentally relevant levels, are able to induce differential DNA methylation in human differentiating adipocytes.
authors.affiliation: Division of Human Nutrition, Wageningen University, The Netherlands; Marine Animal Ecology group, Wageningen University, The Netherlands. Electronic address: Myrthe.vandenDungen@wur.nl.
authors.forename: Myrthe W
authors.initials: MW
authors.lastname: van den Dungen
authors.affiliation: Marine Animal Ecology group, Wageningen University, The Netherlands. Electronic address: Tinka.Murk@wur.nl.
authors.forename: Albertinka J
authors.initials: AJ
authors.lastname: Murk
authors.affiliation: Division of Human Nutrition, Wageningen University, The Netherlands. Electronic address: Dieuwertje.Kok@wur.nl.
authors.forename: Dieuwertje E
authors.initials: DE
authors.lastname: Kok
authors.affiliation: Division of Human Nutrition, Wageningen University, The Netherlands. Electronic address: Wilma.Steegenga@wur.nl.
authors.forename: Wilma T
authors.initials: WT
authors.lastname: Steegenga
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D017738:Alkanesulfonic Acids / Q000633:toxicity; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019175:DNA Methylation / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D005466:Fluorocarbons / Q000633:toxicity; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D059467:Transcriptome / Q000187:drug effects; D014220:Trialkyltin Compounds / Q000633:toxicity
chemical_list: D017738:Alkanesulfonic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons; D000072317:Polychlorinated Dibenzodioxins; D014220:Trialkyltin Compounds; C011559:tributyltin; C076994:perfluorooctane sulfonic acid
keywords: Adipocytes; DNA methylation; Gene expression; Human mesenchymal stem cells; Infinium 450K BeadChip; Persistent organic pollutants (POPs)