Calvanese, VincenzoHorrillo, AngelicaHmadcha, AbdelkrimSuarez-Alvarez, BeatrizFernandez, Agustín FLara, EsterCasado, SaraMenendez, PabloBueno, ClaraGarcia-Castro, JavierRubio, RuthLapunzina, PabloAlaminos, MiguelBorghese, LodovicaTerstegge, StefanieHarrison, Neil JMoore, Harry DBrüstle, OliverLopez-Larrea, CarlosAndrews, Peter WSoria, BernatEsteller, ManelFraga, Mario F2013-02-132013-02-132008-09-29Calvanese V, Horrillo A, Hmadcha A, Suarez-Alvarez B, Fernandez AF, Lara E, et al. Cancer genes hypermethylated in human embryonic stem cells. PLoS ONE; 3(9):e3294http://hdl.handle.net/10668/765Journal Article; Research Support, Non-U.S. Gov't;Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter hypermethylation of tumor suppressor genes (TSGs) in cancer. We report here that silencing of a significant proportion of these TSGs in human embryonic and adult stem cells is associated with promoter DNA hypermethylation. Our results indicate a role for DNA methylation in the control of gene expression in human stem cells and suggest that, for genes repressed by promoter hypermethylation in stem cells in vivo, the aberrant process in cancer could be understood as a defect in establishing an unmethylated promoter during differentiation, rather than as an anomalous process of de novo hypermethylation.enChromatinMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::L Cells (Cell Line)Medical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cell Nucleus::Cell Nucleus Structures::Intranuclear Space::Chromosomes::Chromosome Structures::ChromatinMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA MethylationMedical Subject Headings::Anatomy::Cells::Stem Cells::Embryonic Stem CellsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, DevelopmentalMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic::Gene SilencingMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, NeoplasmMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, NeoplasmMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor::HeLa CellsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::NeoplasmsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene ComponentsMedical Subject Headings::Phenomena and Processes::Physical Phenomena::Time::Time FactorsMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor::U937 CellsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Differentiationresearch article18820729open access10.1371/journal.pone.00032941932-6203PMC2546447