Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation

Boris G. Wilson, Xi Wang, Xiaohua Shen, Elizabeth S. McKenna, Madeleine E. Lemieux, Yoon Jae Cho, Edward C. Koellhoffer, Scott L. Pomeroy, Stuart H. Orkin, Charles W.M. Roberts

Research output: Contribution to journalArticle

333 Scopus citations

Abstract

Epigenetic alterations have been increasingly implicated in oncogenesis. Analysis of Drosophila mutants suggests that Polycomb and SWI/SNF complexes can serve antagonistic developmental roles. However, the relevance of this relationship to human disease is unclear. Here, we have investigated functional relationships between these epigenetic regulators in oncogenic transformation. Mechanistically, we show that loss of the SNF5 tumor suppressor leads to elevated expression of the Polycomb gene EZH2 and that Polycomb targets are broadly H3K27-trimethylated and repressed in SNF5-deficient fibroblasts and cancers. Further, we show antagonism between SNF5 and EZH2 in the regulation of stem cell-associated programs and that Snf5 loss activates those programs. Finally, using conditional mouse models, we show that inactivation of Ezh2 blocks tumor formation driven by Snf5 loss.

Original languageEnglish (US)
Pages (from-to)316-328
Number of pages13
JournalCancer Cell
Volume18
Issue number4
DOIs
StatePublished - Oct 19 2010

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Wilson, B. G., Wang, X., Shen, X., McKenna, E. S., Lemieux, M. E., Cho, Y. J., Koellhoffer, E. C., Pomeroy, S. L., Orkin, S. H., & Roberts, C. W. M. (2010). Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell, 18(4), 316-328. https://doi.org/10.1016/j.ccr.2010.09.006