SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation

Xiaofeng Wang, Ryan S. Lee, Burak H. Alver, Jeffrey R. Haswell, Su Wang, Jakub Mieczkowski, Yotam Drier, Shawn M. Gillespie, Tenley C. Archer, Jennifer N. Wu, Evgeni P. Tzvetkov, Emma C. Troisi, Scott L. Pomeroy, Jaclyn A. Biegel, Michael Y. Tolstorukov, Bradley E. Bernstein, Peter J. Park, Charles W.M. Roberts*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

228 Scopus citations


SMARCB1 (also known as SNF5, INI1, and BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here we show that, despite having indistinguishable mutational landscapes, human rhabdoid tumors exhibit distinct enhancer H3K27ac signatures, which identify remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting-markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers. We show that these retained super-enhancers are essential for rhabdoid tumor survival, including some that are shared by all subtypes, such as SPRY1, and other lineage-specific super-enhancers, such as SOX2 in brain-derived rhabdoid tumors. Taken together, our findings identify a new chromatin-based epigenetic mechanism underlying the tumor-suppressive activity of SMARCB1.

Original languageAmerican English
Pages (from-to)289-295
Number of pages7
JournalNature Genetics
Issue number2
StatePublished - 31 Jan 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature.


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