@article{a6163985ec5749348f3a9efe31b19038,
title = "Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification",
abstract = "Background. Chondrogenesis and subsequent endochondral ossification are processes tightly regulated by the transcription factor Sox9 (SRY-related high mobility group-Box gene 9), but molecular mechanisms underlying this activity remain unclear. Here we report that coactivator-associated arginine methyltransferase 1 (CARM1) regulates chondrocyte proliferation via arginine methylation of Sox9. Results. CARM1-null mice display delayed endochondral ossification and decreased chondrocyte proliferation. Conversely, cartilage development of CARM1 transgenic mice was accelerated. CARM1 specifically methylates Sox9 at its HMG domain in vivo and in vitro. Arg-methylation of Sox9 by CARM1 disrupts interaction of Sox9 with beta-catenin, regulating Cyclin D1 expression and cell cycle progression of chondrocytes. Conclusion. These results establish a role for CARM1 as an important regulator of chondrocyte proliferation during embryogenesis.",
author = "Tatsuo Ito and Neelu Yadav and Jaeho Lee and Takayuki Furumatsu and Satoshi Yamashita and Kenji Yoshida and Noboru Taniguchi and Megumi Hashimoto and Megumi Tsuchiya and Toshifumi Ozaki and Martin Lotz and Bedford, {Mark T.} and Hiroshi Asahara",
note = "Funding Information: We are grateful to Dr. Kazuhisa Nakashima (Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University), Dr. Hidesato Ogawa (Department of Developmental Biology, National Institute for Basic Biology), Dr. Kerri Mowen (Department of Department of Immunology, The Scripps Research Institute), and Dr. Tetsu Osamu (Department of Pathology, School of Medicine, University of California, San Francisco) for providing materials. We also thank Dr. Donghang Cheng (Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center), Dr. Yasuhiko Kawakami (Gene Expression Laboratory, The Salk Institute for Biological Studies), Dr. Hirohito Shimizu, Dr. Teruyuki Tanaka (National Research Institute for Child Health and Development) and Diana C. Brinson (Department of Molecular and Experimental Medicine, The Scripps Research Institute) for technical assistance and discussion. We thank Dr. Marc Ladanyi (Memorial Sloan-Kettering Cancer Center) for reading and comments. We also thank Lilo Creighton and Jacque Quach for staining and FACS scan assays. This work was supported in part by the National Institutes of Health Grant R01 AR050631 (to HA), National Institutes of Health Fellowship F32 AR053442-01A1 (to TI), and National Institutes of Health Grant M01 RR00833 (to ML), National Institutes of Health Grant DK62248 (to MTB)",
year = "2009",
doi = "10.1186/1471-213X-9-47",
language = "English",
volume = "9",
journal = "BMC Developmental Biology",
issn = "1471-213X",
publisher = "BioMed Central",
number = "1",
}