Epigenetic Antagonism between Polycomb and SWI/SNF Complexes during Oncogenic Transformation

被引：518

作者：

Wilson, Boris G. ^{[1
]}

Wang, Xi ^{[1
]}

Shen, Xiaohua ^{[1
]}

McKenna, Elizabeth S. ^{[1
]}

Lemieux, Madeleine E. ^{[1
]}

Cho, Yoon-Jae ^{[2
]}

Koellhoffer, Edward C. ^{[1
]}

Pomeroy, Scott L. ^{[2
]}

Orkin, Stuart H. ^{[1
,3
,4
]}

Roberts, Charles W. M. ^{[1
]}

机构：

[1] Harvard Univ, Div Hematol Oncol, Childrens Hosp Boston,Dept Pediat, Dept Pediat Oncol,Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA

[2] Childrens Hosp Boston, Dept Neurol, Boston, MA 02115 USA

[3] Howard Hughes Med Inst, Boston, MA 02115 USA

[4] Harvard Stem Cell Inst, Boston, MA 02115 USA

来源：

CANCER CELL | 2010年 / 18卷 / 04期

关键词：

EMBRYONIC STEM-CELLS; TUMOR-SUPPRESSOR GENE; GROUP PROTEIN EZH2; RHABDOID TUMOR; DEVELOPMENTAL REGULATORS; GENOMIC INSTABILITY; SELF-RENEWAL; CANCER; CHROMATIN; DROSOPHILA;

D O I：

10.1016/j.ccr.2010.09.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：316 / 328

页数：13

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[1] The Drosophila BRM complex facilitates global transcription by RNA polymerase II [J].