Cancer Cell
Volume 3, Issue 1, January 2003, Pages 89-95
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Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene

https://doi.org/10.1016/S1535-6108(02)00234-9Get rights and content
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Abstract

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.

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These authors contributed equally to this work.