Abstract A36: Interaction of the MYC oncoprotein with the tumor suppressive SWI/SNF complex member INI1

The MYC oncogene is a key driver of cellular transformation that is deregulated in more than half of all human cancers. The transcriptional regulatory function of MYC and the wide spectrum of biological processes it mediates are critically tied to its chromatin interactors and epigenetic context. MYC is linked to chromatin remodeling through its interaction with INI1 (SMARCB1/hSNF5/BAF47), a core member of the SWI/SNF complex and a potent tumour suppressor. Recent sequencing efforts in many cancer types also identified frequent mutations in other members of this complex. However, the mechanistic understanding of the SWI/SNF complex in contributing to oncogenesis and its functional and molecular interaction with MYC remain unclear. Herein, we provide a comprehensive characterization of the MYC-INI1 interaction. We demonstrate their direct interaction and extensively delineate their minimal regions of interaction, corresponding to functionally important regions of MYC (leucine zipper) and INI1 (Repeats I and II). Genome-wide analysis reveals that INI1 and other SWI/SNF complex members share significant portions of MYC DNA-binding regions and target genes. Network analysis demonstrates MYC interaction with the SWI/SNF complex and an extended network of shared interactors belonging to additional chromatin regulatory complexes. Collectively, our findings provide significant insight into the interaction of MYC and INI1 at the level of protein-protein and protein-chromatin interactions. Citation Format: William B. Tu, Angelina Stojanova, Romina Ponzielli, Max Kotlyar, Pak-Kei Chan, Paul C. Boutros, Fereshteh Khosravi, Igor Jurisica, Brian Raught, Linda Z. Penn. Interaction of the MYC oncoprotein with the tumor suppressive SWI/SNF complex member INI1. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A36.