title: Cancer genes hypermethylated in human embryonic stem cells.
abstract: 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.
authors.affiliation: Cancer Epigenetics Group, Spanish National Cancer Research Centre, CNIO, Madrid, Spain.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Calvanese
authors.forename: Angelica
authors.initials: A
authors.lastname: Horrillo
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Hmadcha
authors.forename: Beatriz
authors.initials: B
authors.lastname: Suarez-Alvarez
authors.forename: Agustín F
authors.initials: AF
authors.lastname: Fernandez
authors.forename: Ester
authors.initials: E
authors.lastname: Lara
authors.forename: Sara
authors.initials: S
authors.lastname: Casado
authors.forename: Pablo
authors.initials: P
authors.lastname: Menendez
authors.forename: Clara
authors.initials: C
authors.lastname: Bueno
authors.forename: Javier
authors.initials: J
authors.lastname: Garcia-Castro
authors.forename: Ruth
authors.initials: R
authors.lastname: Rubio
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
authors.forename: Miguel
authors.initials: M
authors.lastname: Alaminos
authors.forename: Lodovica
authors.initials: L
authors.lastname: Borghese
authors.forename: Stefanie
authors.initials: S
authors.lastname: Terstegge
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Harrison
authors.forename: Harry D
authors.initials: HD
authors.lastname: Moore
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopez-Larrea
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrews
authors.forename: Bernat
authors.initials: B
authors.lastname: Soria
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.forename: Mario F
authors.initials: MF
authors.lastname: Fraga
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D052138:Genes, Neoplasm; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D013997:Time Factors; D020298:U937 Cells
chemical_list: D002843:Chromatin