Downloaded from http://perspectivesinmedicine.cshlp.org/ at Cold Spring Harbor Laboratory Library on July 14, 2016 - Published by Cold Spring Harbor Laboratory Press The Many Roles of BAF (mSWI/SNF) and PBAF Complexes in Cancer Courtney Hodges, Jacob G. Kirkland, and Gerald R. Crabtree Departments of Pathology, Developmental Biology, and Genetics, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305 Correspondence:
[email protected] During the last decade, a host of epigenetic mechanisms were found to contribute to cancer and other human diseases. Several genomic studies have revealed that 20% of malignan- cies have alterations of the subunits of polymorphic BRG-/BRM-associated factor (BAF) and Polybromo-associated BAF (PBAF) complexes, making them among the most frequently mutated complexes in cancer. Recurrent mutations arise in genes encoding several BAF/ PBAF subunits, including ARID1A, ARID2, PBRM1, SMARCA4, and SMARCB1. These sub- units share some degree of conservation with subunits from related adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in model organisms, in which a large body of work provides insight into their roles in cancer. Here, we review the roles of BAF- and PBAF-like complexes in these organisms, and relate these findings to recent discoveries in cancer epigenomics. We review several roles of BAF and PBAF complexes in cancer, includ- ing transcriptional regulation, DNA repair, and regulation of chromatin architecture and topology.More recent results highlight the need for new techniques to study these complexes. EPIGENOMICS IN CANCER the full spectrum of achievable cell-type diver- sity for the organism. Because epigenetic regu- roadly defined, epigenetic factors contrib- lation contributes to cell-type functional spe- Bute to the expression state of the genome cialization, it is essential for multicellular life.