Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification

Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
BMC Developmental Biology (Impact Factor: 2.67). 10/2009; 9(1):47. DOI: 10.1186/1471-213X-9-47
Source: PubMed


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.
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.
These results establish a role for CARM1 as an important regulator of chondrocyte proliferation during embryogenesis.

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    • "The structure of the HMG box and the residues flanking methylation site of Sox2 are conserved among Sox family members (Supporting information Figure S7) [20]. Recently, CARM1 was reported to methylate Sox9, a Sox family member implicated in chondrogenesis and sex determination [21]. Therefore, it is reasonable to hypothesize that the CARM1-mediated arginine methylation is a prevalent modulation mechanism throughout the Sox family. "
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