Cancer genes hypermethylated in human embryonic stem cells

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...

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Bibliographic Details
Published in:PloS one 2008-09, Vol.3 (9), p.e3294-e3294
Main Authors: Calvanese, Vincenzo, Horrillo, Angelica, Hmadcha, Abdelkrim, Suarez-Alvarez, Beatriz, Fernandez, Agustín F, Lara, Ester, Casado, Sara, Menendez, Pablo, Bueno, Clara, Garcia-Castro, Javier, Rubio, Ruth, Lapunzina, Pablo, Alaminos, Miguel, Borghese, Lodovica, Terstegge, Stefanie, Harrison, Neil J, Moore, Harry D, Brüstle, Oliver, Lopez-Larrea, Carlos, Andrews, Peter W, Soria, Bernat, Esteller, Manel, Fraga, Mario F
Format: Article
Language:English
Subjects:
Aberration
Cancer
Cancer genetics
Cell Differentiation
Cell Line
Chromatin
Chromatin - metabolism
Deoxyribonucleic acid
Developmental Biology/Stem Cells
DNA
DNA Methylation
Embryo cells
Embryonic stem cells
Embryonic Stem Cells - cytology
Embryos
Epigenetics
Gene expression
Gene Expression Regulation, Developmental
Gene Silencing
Genes
Genes, Neoplasm
Genetic aspects
Genetics and Genomics/Epigenetics
HeLa Cells
HL-60 Cells
Humans
Methylation
Neoplasms - genetics
Neoplasms - metabolism
Oncology
Promoter Regions, Genetic
Stem cells
Time Factors
Tumor suppressor genes
U937 Cells
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0003294