Weissmiller, April M.Wang, JingLorey, Shelly L.Howard, Gregory C.Martinez, ErnestLiu, QiTansey, William P.2020-04-072020-04-072019-05-01Weissmiller, A. M., Wang, J., Lorey, S. L., Howard, G. C., Martinez, E., Liu, Q., & Tansey, W. P. (2019). Inhibition of MYC by the SMARCB1 tumor suppressor. Nature communications, 10(1), 2014. https://doi.org/10.1038/s41467-019-10022-52041-1723https://ir.vanderbilt.edu/xmlui/handle/1803/9902SMARCB1 encodes the SNF5 subunit of the SWI/SNF chromatin remodeler. SNF5 also interacts with the oncoprotein transcription factor MYC and is proposed to stimulate MYC activity. The concept that SNF5 is a coactivator for MYC, however, is at odds with its role as a tumor-suppressor, and with observations that loss of SNF5 leads to activation of MYC target genes. Here, we reexamine the relationship between MYC and SNF5 using biochemical and genome-wide approaches. We show that SNF5 inhibits the DNA-binding ability of MYC and impedes target gene recognition by MYC in cells. We further show that MYC regulation by SNF5 is separable from its role in chromatin remodeling, and that reintroduction of SNF5 into SMARCB1-null cells mimics the primary transcriptional effects of MYC inhibition. These observations reveal that SNF5 antagonizes MYC and provide a mechanism to explain how loss of SNF5 can drive malignancy.en-USThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holderSWI/SNF COMPLEXC-MYCBAF COMPLEXESTRANSCRIPTIONCHROMATINARRESTTUMORIGENESISACTIVATIONINITIATIONINTERACTSArticle10.1038/s41467-019-10022-5