| Summary: | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 <it>in vivo </it>and <it>in vitro</it>. Arg-methylation of Sox9 by CARM1 disrupts interaction of Sox9 with beta-catenin, regulating <it>Cyclin D1 </it>expression and cell cycle progression of chondrocytes.</p> <p>Conclusion</p> <p>These results establish a role for CARM1 as an important regulator of chondrocyte proliferation during embryogenesis.</p>
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