Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification

Tatsuo Ito, Neelu Yadav, Jaeho Lee, Takayuki Furumatsu, Satoshi Yamashita, Kenji Yoshida, Noboru Taniguchi, Megumi Hashimoto, Megumi Tsuchiya, Toshihumi Ozaki, Martin Lotz, Mark T. Bedford, Hiroshi Asahara

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Article number47
JournalBMC Developmental Biology
Volume9
Issue number1
DOIs
Publication statusPublished - 2009

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Osteogenesis
Chondrocytes
Methylation
Chondrogenesis
Cyclin D1
beta Catenin
Transgenic Mice
Cartilage
Embryonic Development
Arginine
human PRMT2 protein
coactivator-associated arginine methyltransferase 1
Cell Cycle
Transcription Factors
Genes

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification. / Ito, Tatsuo; Yadav, Neelu; Lee, Jaeho; Furumatsu, Takayuki; Yamashita, Satoshi; Yoshida, Kenji; Taniguchi, Noboru; Hashimoto, Megumi; Tsuchiya, Megumi; Ozaki, Toshihumi; Lotz, Martin; Bedford, Mark T.; Asahara, Hiroshi.

In: BMC Developmental Biology, Vol. 9, No. 1, 47, 2009.

Research output: Contribution to journalArticle

Ito, T, Yadav, N, Lee, J, Furumatsu, T, Yamashita, S, Yoshida, K, Taniguchi, N, Hashimoto, M, Tsuchiya, M, Ozaki, T, Lotz, M, Bedford, MT & Asahara, H 2009, 'Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification', BMC Developmental Biology, vol. 9, no. 1, 47. https://doi.org/10.1186/1471-213X-9-47
Ito, Tatsuo ; Yadav, Neelu ; Lee, Jaeho ; Furumatsu, Takayuki ; Yamashita, Satoshi ; Yoshida, Kenji ; Taniguchi, Noboru ; Hashimoto, Megumi ; Tsuchiya, Megumi ; Ozaki, Toshihumi ; Lotz, Martin ; Bedford, Mark T. ; Asahara, Hiroshi. / Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification. In: BMC Developmental Biology. 2009 ; Vol. 9, No. 1.
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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.",
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AU - Yoshida, Kenji

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