Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene

Kurtis E. Bachman, Ben Ho Park, Ina Rhee, Harith Rajagopalan, James G. Herman, Stephen B. Baylin, Kenneth W. Kinzler, Bert Vogelstein

Research output: Contribution to journalArticlepeer-review

345 Scopus citations


We attempted to answer two central questions about epigenetic silencing of the tumor suppressor gene p16INK4a in this study: (1) whether the maintenance of associated histone modifications is dependent on DNA methylation and (2) whether such histone modifications can occur prior to DNA methylation. By coupling chromatin immunoprecipitation with gene targeting and the analysis of specific alleles, we found that elimination of DNA methylation from a p16INK4a allele resulted in profound changes in surrounding histones. After continued passage of such cells, methylation of histone H3 lysine-9 occurred in conjunction with re-silencing in the absence of DNA methylation. These results have important implications for understanding the biochemical events underlying the silencing of tumor suppressor genes and the resultant growth suppression.

Original languageEnglish (US)
Pages (from-to)89-95
Number of pages7
JournalCancer cell
Issue number1
StatePublished - Jan 2003

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research


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