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Cancer Genes Hypermethylated in Human Embryonic Stem Cells

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posted on 29.09.2008, 02:39 by Vincenzo Calvanese, Angelica Horrillo, Abdelkrim Hmadcha, Beatriz Suárez-Álvarez, Agustin F. Fernandez, Ester Lara, Sara Casado, Pablo Menendez, Clara Bueno, Javier Garcia-Castro, Ruth Rubio, Pablo Lapunzina, Miguel Alaminos, Lodovica Borghese, Stefanie Terstegge, Neil J. Harrison, Harry D. Moore, Oliver Brüstle, Carlos López-Larrea, Peter W. Andrews, Bernat Soria, Manel Esteller, Mario F. Fraga

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.

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