Methyltransferase Recruitment and DNA Hypermethylation of Target Promoters by an Oncogenic Transcription Factor

DOI Web Site 被引用文献19件
  • Luciano Di Croce
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
  • Veronica A. Raker
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
  • Massimo Corsaro
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
  • Francesco Fazi
    Department of Histology and Medical Embryology,
  • Mirco Fanelli
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
  • Mario Faretta
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
  • Francois Fuks
    Wellcome/CRC Institute and Department of Pathology, Cambridge University, Cambridge, UK.
  • Francesco Lo Coco
    Department of Cellular Biotechnology and Hematology, University of Rome, “La Sapienza,” Rome, Italy.
  • Tony Kouzarides
    Wellcome/CRC Institute and Department of Pathology, Cambridge University, Cambridge, UK.
  • Clara Nervi
    Department of Histology and Medical Embryology,
  • Saverio Minucci
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
  • Pier Giuseppe Pelicci
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.

抄録

<jats:p>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.</jats:p>

収録刊行物

  • Science

    Science 295 (5557), 1079-1082, 2002-02-08

    American Association for the Advancement of Science (AAAS)

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