RT Journal Article
T1 DNA methylation reprogramming of human cancer cells by expression of a plant 5-methylcytosine DNA glycosylase.
A1 Morales-Ruiz, Teresa
A1 Garcia-Ortiz, Maria Victoria
A1 Devesa-Guerra, Ivan
A1 Raya-Ruiz, Laura
A1 Tejedor, Juan R
A1 Bayon, Gustavo F
A1 Sierra, Marta I
A1 Fraga, Mario F
A1 Ariza, Rafael R
A1 Roldan-Arjona, Teresa
K1 DNA demethylation
K1 DNA methylation
K1 Epigenetics
K1 Base excision repair
K1 Colon cancer
AB Patterns of DNA methylation, an important epigenetic modification involved in gene silencing and development, are disrupted in cancer cells. Understanding the functional significance of aberrant methylation in tumors remains challenging, due in part to the lack of suitable tools to actively modify methylation patterns. DNA demethylation caused by mammalian DNA methyltransferase inhibitors is transient and replication-dependent, whereas that induced by TET enzymes involves oxidized 5mC derivatives that perform poorly understood regulatory functions. Unlike animals, plants possess enzymes that directly excise unoxidized 5mC from DNA, allowing restoration of unmethylated C through base excision repair. Here, we show that expression of Arabidopsis 5mC DNA glycosylase DEMETER (DME) in colon cancer cells demethylates and reactivates hypermethylated silenced loci. Interestingly, DME expression causes genome-wide changes that include both DNA methylation losses and gains, and partially restores the methylation pattern observed in normal tissue. Furthermore, such methylome reprogramming is accompanied by altered cell cycle responses and increased sensibility to anti-tumor drugs, decreased ability to form colonospheres, and tumor growth impairment in vivo. Our study shows that it is possible to reprogram a human cancer DNA methylome by expression of a plant DNA demethylase.
PB Taylor & Francis
YR 2018
FD 2018-02-07
LK http://hdl.handle.net/10668/11902
UL http://hdl.handle.net/10668/11902
LA en
NO Morales-Ruiz T, García-Ortiz MV, Devesa-Guerra I, Raya-Ruiz L, Tejedor JR, Bayón GF, et al. DNA methylation reprogramming of human cancer cells by expression of a plant 5-methylcytosine DNA glycosylase. Epigenetics. 2018;13(1):95-107
DS RISalud
RD Apr 7, 2025