title: CARM1 methylates chromatin remodeling factor BAF155 to enhance tumor progression and metastasis.
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.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Zibo
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Meyer
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Saha
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Menggang
authors.initials: M
authors.lastname: Yu
authors.affiliation: Cell Signaling Technology, Danvers, MA 01923, USA.
authors.forename: Ailan
authors.initials: A
authors.lastname: Guo
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Kari B
authors.initials: KB
authors.lastname: Wisinski
authors.affiliation: Department of Pathology, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: J Wesley
authors.initials: JW
authors.lastname: Pike
authors.affiliation: Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Statistics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Paul
authors.initials: P
authors.lastname: Ahlquist
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: wxu@oncology.wisc.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C101681:SMARCC1 protein, human; C491090:Smarcc1 protein, mouse; D014157:Transcription Factors; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1