Journal
CANCER CELL
Volume 33, Issue 6, Pages 1128-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2018.05.002
Keywords
-
Categories
Funding
- NIH [1DP2CA195762-01, 5 T32 GM095450-04]
- American Cancer Society [RSG-14-051-01-DMC]
- Pew-Stewart Scholars in Cancer Research Grant
- Alex's Lemonade Stand Foundation Young Investigator Award
- Harvard University Graduate School of Arts and Sciences (GSAS) Fellowship
- NATIONAL CANCER INSTITUTE [ZIABC011002, ZIABC011734] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM095450] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate an SS transcriptional signature that we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated repression and activate bivalent genes. Upon suppression of SS18-SSX, reassembly of BAF47 restores enhancer activation, but is not required for proliferative arrest. These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available