Inhibition of MYC by the SMARCB1 tumor suppressor

We report that the protein encoded by the SMARCB1 gene, SNF5, is capable of inhibiting MYC binding in vitro and in a malignant rhabdoid tumor (MRT) cell line. By comparing the effects of reintroduction of SNF5 with genetic inhibition of MYC (OMOMYC) on multiple aspects of chromatin remodeling and transcription in MRT cells, we show that regulation of MYC binding by SNF5 is not connected to the role of SNF5 in chromatin remodeling, but instead is responsible for controlling RNA polymerase pause release during transcription. Our data reveal that SNF5 negatively regulates MYC function and may explain how loss of SNF5 can lead to rapid tumorigenesis. Overall design: The G401 MRT cell line was transduced with lentiviral vectors expressing tetracycline (TET)-inducible version of EGFP, SNF5, or OMOMYC. Immediately following selection, each group of transduced cells were treated with 1ug/ml doxycycline for 24 hours. All ChIP-seq, ATAC-seq, and PRO-Seq experiments were performed at the 24 hour timepoint.