CARM1 methylates chromatin remodeling factor BAF155 to enhance tumor progression and metastasis.

Lu Wang, Zibo Zhao, Mark B Meyer, Sandeep Saha, Menggang Yu, Ailan Guo, Kari B Wisinski, Wei Huang, Weibo Cai, J Wesley Pike, Ming Yuan, Paul Ahlquist, Wei Xu

Cancer cell 2014 Jan 13

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Coactivator-associated arginine methyltransferase 1 (CARM1), a coactivator for various cancer-relevant transcription factors, is overexpressed in breast cancer. To elucidate the functions of CARM1 in tumorigenesis, we knocked out CARM1 from several breast cancer cell lines using Zinc-Finger Nuclease technology, which resulted in drastic phenotypic and biochemical changes. The CARM1 KO cell lines enabled identification of CARM1 substrates, notably the SWI/SNF core subunit BAF155. Methylation of BAF155 at R1064 was found to be an independent prognostic biomarker for cancer recurrence and to regulate breast cancer cell migration and metastasis. Furthermore, CARM1-mediated BAF155 methylation affects gene expression by directing methylated BAF155 to unique chromatin regions (e.g., c-Myc pathway genes). Collectively, our studies uncover a mechanism by which BAF155 acquires tumorigenic functions via arginine methylation. Copyright © 2014 Elsevier Inc. All rights reserved.

Citation

Lu Wang, Zibo Zhao, Mark B Meyer, Sandeep Saha, Menggang Yu, Ailan Guo, Kari B Wisinski, Wei Huang, Weibo Cai, J Wesley Pike, Ming Yuan, Paul Ahlquist, Wei Xu. CARM1 methylates chromatin remodeling factor BAF155 to enhance tumor progression and metastasis. Cancer cell. 2014 Jan 13;25(1):21-36