Cancer Cell
Volume 25, Issue 1, 13 January 2014, Pages 21-36
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Article
CARM1 Methylates Chromatin Remodeling Factor BAF155 to Enhance Tumor Progression and Metastasis

https://doi.org/10.1016/j.ccr.2013.12.007Get rights and content
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Highlights

  • Knockout of CARM1 Using ZFN in Breast Cancer Cells

  • Identification of BAF155 as a Novel CARM1 Substrate

  • Methylation of BAF155 Promotes Tumor Growth and Metastasis

  • Methylated BAF155 Gains Unique Chromatin Association

Summary

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.

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