Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification.
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.


CONCLUSIONS
These results establish a role for CARM1 as an important regulator of chondrocyte proliferation during embryogenesis.
Ito
Tatsuo
T
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. itot@mskcc.org
Yadav
Neelu
N
Lee
Jaeho
J
Furumatsu
Takayuki
T
Yamashita
Satoshi
S
Yoshida
Kenji
K
Taniguchi
Noboru
N
Hashimoto
Megumi
M
Tsuchiya
Megumi
M
Ozaki
Toshifumi
T
Lotz
Martin
M
Bedford
Mark T
MT
Asahara
Hiroshi
H
D000818:Animals; D001842:Bone and Bones / Q000196:embryology; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism; D020219:Chondrogenesis; D055785:Gene Knockdown Techniques; D006132:Growth Plate / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010012:Osteogenesis; D055758:SOX9 Transcription Factor / Q000378:metabolism
D053468:CARD Signaling Adaptor Proteins; C496467:Card11 protein, mouse; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; C426242:CARD11 protein, human; D006162:Guanylate Cyclase