CARM1 Methylates Chromatin Remodeling Factor BAF155 to Enhance Tumor Progression and Metastasis
Menée sur des lignées cellulaires, cette étude met en évidence des mécanismes par lesquels, en méthylant le gène BAF115, la méthyltransférase CARM1 favorise la croissance tumorale et le processus métastatique d'un cancer du sein
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.
"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
Cancer cell , résumé, 2013