Binding of TMPRSS2-ERG to BAF Chromatin Remodeling Complexes Mediates Prostate Oncogenesis

被引：81

作者：

Sandoval, Gabriel J. ^{[1
,2
,3
,4
]}

Pulice, John L. ^{[2
,3
,4
]}

Pakula, Hubert ^{[5
,6
]}

Schenone, Monica ^{[4
]}

Takeda, David Y. ^{[1
,2
,4
]}

Pop, Marius ^{[1
,2
,4
]}

Boulay, Gaylor ^{[4
,7
,8
]}

Williamson, Kaylyn E. ^{[2
,3
,4
]}

McBride, Matthew J. ^{[2
,3
,4
,9
]}

Pan, Joshua ^{[2
,3
,4
]}

St Pierre, Roodolph ^{[2
,3
,9
]}

Hartman, Emily ^{[4
]}

Garraway, Levi A. ^{[1
,2
,4
]}

Carr, Steven A. ^{[4
]}

Rivera, Miguel N. ^{[4
,7
,8
]}

Li, Zhe ^{[5
,6
]}

Ronco, Lucienne ^{[4
]}

Hahn, William C. ^{[1
,2
,4
]}

Kadoch, Cigall ^{[2
,3
,4
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[4] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[5] Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA

[6] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[7] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[8] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA

[9] Harvard Med Sch, Chem Biol Program, Boston, MA USA

来源：

MOLECULAR CELL | 2018年 / 71卷 / 04期

关键词：

ETS GENE FUSIONS; TRANSCRIPTION FACTORS; ANDROGEN RECEPTOR; CANCER; ERG; PROTEIN; IDENTIFICATION; FAMILY; ETV1; UBIQUITINATION;

D O I：

10.1016/j.molcel.2018.06.040

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Chromosomal rearrangements resulting in the fusion of TMPRSS2, an androgen-regulated gene, and the ETS family transcription factor ERG occur in over half of prostate cancers. However, the mechanism by which ERG promotes oncogenic gene expression and proliferation remains incompletely understood. Here, we identify a binding interaction between ERG and the mammalian SWI/SNF (BAF) ATP-dependent chromatin remodeling complex, which is conserved among other oncogenic ETS factors, including ETV1, ETV4, and ETV5. We find that ERG drives genome-wide retargeting of BAF complexes in a manner dependent on binding of ERG to the ETS DNA motif. Moreover, ERG requires intact BAF complexes for chromatin occupancy and BAF complex ATPase activity for target gene regulation. In a prostate organoid model, BAF complexes are required for ERG-mediated basal-to-luminal transition, a hallmark of ERG activity in prostate cancer. These observations suggest a fundamental interdependence between ETS transcription factors and BAF chromatin remodeling complexes in cancer.

引用

页码：554 / +

页数：20

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