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

First Author  Wilson BG Year  2010
Journal  Cancer Cell Volume  18
Issue  4 Pages  316-28
PubMed ID  20951942 Mgi Jnum  J:165554
Mgi Id  MGI:4837755 Doi  10.1016/j.ccr.2010.09.006
Citation  Wilson BG, et al. (2010) Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell 18(4):316-28
abstractText  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.
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