@article{2ee8e83389d4408ab543de4a2773fd53,
title = "Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes",
abstract = "Histone modification, a critical step for epigenetic regulation, is an important modulator of biological events. Sox9 is a transcription factor critical for endochondral ossification; however, proof of its epigenetic regulation remains elusive. Here we identify AT-rich interactive domain 5b (Arid5b) as a transcriptional co-regulator of Sox9. Arid5b physically associates with Sox9 and synergistically induces chondrogenesis. Growth of Arid5b-/- mice is retarded with delayed endochondral ossification. Sox9-dependent chondrogenesis is attenuated in Arid5b-deficient cells. Arid5b recruits Phf2, a histone lysine demethylase, to the promoter region of Sox9 target genes and stimulates H3K9me2 demethylation of these genes. In the promoters of chondrogenic marker genes, H3K9me2 levels are increased in Arid5b-/- chondrocytes. Finally, we show that Phf2 knockdown inhibits Sox9-induced chondrocyte differentiation. Our findings establish an epigenomic mechanism of skeletal development, whereby Arid5b promotes chondrogenesis by facilitating Phf2-mediated histone demethylation of Sox9-regulated chondrogenic gene promoters.",
author = "Kenji Hata and Rikako Takashima and Katsuhiko Amano and Koichiro Ono and Masako Nakanishi and Michiko Yoshida and Makoto Wakabayashi and Akio Matsuda and Yoshinobu Maeda and Yutaka Suzuki and Sumio Sugano and Whitson, {Robert H.} and Riko Nishimura and Toshiyuki Yoneda",
note = "Funding Information: We thank Benoit de Crombrugghe for the Col2a1 promoter and Atsushi Miyawaki for the Venus construct. We are grateful to Atsushi Baba, Fumiaki Ohtake, Yuuki Imai and Shigeaki Kato for their expert technical assistance and for providing the anti-Phf2 antibody. This work was supported in part by Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research (K.H. and R.N.), ''Challenge to Intractable Oral Diseases'' (K.H.), The Uehara Memorial Foundation (K.H. and R.N.), Senri Life Science Foundation (K.H.), and The Nakatomi Foundation (K.H.). This investigation was supported in part by The Mochida Memorial Foundation for Medical and Pharmaceutical Research (K.H.). Funding Information: We thank Benoit de Crombrugghe for the Col2a1 promoter and Atsushi Miyawaki for the Venus construct. We are grateful to Atsushi Baba, Fumiaki Ohtake, Yuuki Imai and Shigeaki Kato for their expert technical assistance and for providing the anti-Phf2 antibody. This work was supported in part by Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research (K.H. and R.N.), {\textquoteleft}Challenge to Intractable Oral Diseases{\textquoteright} (K.H.), The Uehara Memorial Foundation (K.H. and R.N.), Senri Life Science Foundation (K.H.), and The Nakatomi Foundation (K.H.). This investigation was supported in part by The Mochida Memorial Foundation for Medical and Pharmaceutical Research (K.H.). Publisher Copyright: {\textcopyright} 2013 Macmillan Publishers Limited. All rights reserved.",
year = "2013",
month = nov,
day = "26",
doi = "10.1038/ncomms3850",
language = "English",
volume = "4",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}