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

doi:10.1016/j.ccr.2013.12.007

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

Cancer Cell. 2014 Jan 13;25(1):21-36. doi: 10.1016/j.ccr.2013.12.007.

Authors

Lu Wang¹, Zibo Zhao¹, Mark B Meyer², Sandeep Saha³, Menggang Yu³, Ailan Guo⁴, Kari B Wisinski⁵, Wei Huang⁶, Weibo Cai⁷, J Wesley Pike², Ming Yuan⁸, Paul Ahlquist⁹, Wei Xu¹⁰

Affiliations

¹ McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.
² Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
³ Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53706, USA.
⁴ Cell Signaling Technology, Danvers, MA 01923, USA.
⁵ Department of Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
⁶ Department of Pathology, University of Wisconsin-Madison, Madison, WI 53706, USA.
⁷ Department of Radiology, University of Wisconsin-Madison, Madison, WI 53706, USA.
⁸ Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Statistics, University of Wisconsin-Madison, Madison, WI 53706, USA.
⁹ McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA; Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53706, USA; Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI 53706, USA.
¹⁰ McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: wxu@oncology.wisc.edu.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Blotting, Western
Breast Neoplasms / genetics
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Cell Line, Tumor
Chromatin Assembly and Disassembly
DNA Methylation
Disease Progression
Female
Gene Expression Regulation, Neoplastic / physiology*
Humans
Mice
Mice, Knockout
Neoplasm Invasiveness / genetics
Neoplasm Invasiveness / pathology
Oligonucleotide Array Sequence Analysis
Protein-Arginine N-Methyltransferases / metabolism*
Tissue Array Analysis
Transcription Factors / metabolism*

Substances

SMARCC1 protein, human
Smarcc1 protein, mouse
Transcription Factors
Protein-Arginine N-Methyltransferases
coactivator-associated arginine methyltransferase 1

Associated data

GEO/GSE52964

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding