RT Journal Article SR Electronic T1 Hypermethylation and Carcinogenesis JF Science's STKE JO Sci. STKE FD American Association for the Advancement of Science SP tw67 OP tw67 DO 10.1126/stke.2002.119.tw67 VO 2002 IS 119 YR 2002 UL http://stke.sciencemag.org/content/2002/119/tw67.abstract AB In cancer cells, abnormal methylation patterns of DNA sequences are often present. By examining the role of the PML-RAR fusion gene, a well-studied translocation in leukemia, Di Croce et al. demonstrate that transcriptional silencing in cancer cells can occur through the recruitment of a DNA methyltransferase (Dnmt) by the PML-RAR fusion protein. Recruitment of Dnmts results in the hypermethylation of a PML-RAR target gene, RARĪ²2. In the presence of PML-RAR and Dnmt, cell differentiation was blocked, but this block could be overcome by administration of retinoic acid. Hence, transcription factors associated with neoplasia can function in methylation-linked silencing of genes important for growth and differentiation. Furthermore, the work shows that a genetic change in cancer can induce epigenetic gene silencing. L. Di Croce, V. A. Raker, M. Corsaro, F. Fazi, M. Fanelli, M. Faretta, F. Fuks, F. Lo Coco, T. Kouzarides, C. Nervi, S. Minucci, P. G. Pelicci, Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science 295, 1079-1082 (2002). [Abstract] [Full Text]