Transcriptomics

Dataset Information

4

Epigenetic antagonism between Snf5 and Ezh2 during oncogenic transformation


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. Mouse Embryonic Fibroblasts (MEFs) conditionally inactivated for Ezh2, Snf5 and Ezh2, or from control WT MEFs were used to evaluated epigenetic antagonism between Snf5 and Ezh2 in the control of gene expression programs. Snf5-deficient lymphoma samples and control CD8+ WT T-cells were used to evaluate genetic programs misregulated by Snf5 inactivation during tumorigenesis. RNA was isolated from each of these samples and used for gene expression profiling on Affymetrix arrays.

ORGANISM(S): Mus musculus  

SUBMITTER: Boris G. Wilson   Charles Roberts 

PROVIDER: E-GEOD-23656 | ArrayExpress | 2010-10-19

SECONDARY ACCESSION(S): GSE23656PRJNA133129

REPOSITORIES: GEO, ArrayExpress

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Publications

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

Wilson Boris G BG   Wang Xi X   Shen Xiaohua X   McKenna Elizabeth S ES   Lemieux Madeleine E ME   Cho Yoon-Jae YJ   Koellhoffer Edward C EC   Pomeroy Scott L SL   Orkin Stuart H SH   Roberts Charles W M CW  

Cancer cell 20101001 4


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 EZH  ...[more]

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