DNA methylation of tumor suppressor genes is a frequent mechanism of transcriptional silencing in cancer. The molecular mechanisms underlying the specificity of methylation are unknown. We report here that the leukemia-promoting PML-RAR fusion protein induces gene hypermethylation and silencing by recruiting DNA methyltransferases to target promoters and that hypermethylation contributes to its leukemogenic potential. Retinoic acid treatment induces promoter demethylation, gene reexpression, and reversion of the transformed phenotype. These results establish a mechanistic link between genetic and epigenetic changes during transformation and suggest that hypermethylation contributes to the early steps of carcinogenesis.

Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor / L., Di Croce; V. A., Raker; M., Corsaro; Fazi, Francesco; M., Fanelli; M., Faretta; F., Fuks; F., Lo Coco; T., Kouzarides; Nervi, Clara; S., Minucci; P. G., Pelicci. - In: SCIENCE. - ISSN 0036-8075. - STAMPA. - 295:5557(2002), pp. 1079-1082. [10.1126/science.1065173]

Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor

FAZI, Francesco;NERVI, Clara;
2002

Abstract

DNA methylation of tumor suppressor genes is a frequent mechanism of transcriptional silencing in cancer. The molecular mechanisms underlying the specificity of methylation are unknown. We report here that the leukemia-promoting PML-RAR fusion protein induces gene hypermethylation and silencing by recruiting DNA methyltransferases to target promoters and that hypermethylation contributes to its leukemogenic potential. Retinoic acid treatment induces promoter demethylation, gene reexpression, and reversion of the transformed phenotype. These results establish a mechanistic link between genetic and epigenetic changes during transformation and suggest that hypermethylation contributes to the early steps of carcinogenesis.
2002
01 Pubblicazione su rivista::01a Articolo in rivista
Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor / L., Di Croce; V. A., Raker; M., Corsaro; Fazi, Francesco; M., Fanelli; M., Faretta; F., Fuks; F., Lo Coco; T., Kouzarides; Nervi, Clara; S., Minucci; P. G., Pelicci. - In: SCIENCE. - ISSN 0036-8075. - STAMPA. - 295:5557(2002), pp. 1079-1082. [10.1126/science.1065173]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/254632
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