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 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.
Calvanese
Vincenzo
V
Cancer Epigenetics Group, Spanish National Cancer Research Centre, CNIO, Madrid, Spain.
Horrillo
Angelica
A
Hmadcha
Abdelkrim
A
Suarez-Alvarez
Beatriz
B
Fernandez
Agustín F
AF
Lara
Ester
E
Casado
Sara
S
Menendez
Pablo
P
Bueno
Clara
C
Garcia-Castro
Javier
J
Rubio
Ruth
R
Lapunzina
Pablo
P
Alaminos
Miguel
M
Borghese
Lodovica
L
Terstegge
Stefanie
S
Harrison
Neil J
NJ
Moore
Harry D
HD
Brüstle
Oliver
O
Lopez-Larrea
Carlos
C
Andrews
Peter W
PW
Soria
Bernat
B
Esteller
Manel
M
Fraga
Mario F
MF
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
D002843:Chromatin