Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes

被引：79

作者：

Hata, Kenji ^{[1
]}

Takashima, Rikako ^{[1
,2
]}

Amano, Katsuhiko ^{[1
]}

Ono, Koichiro ^{[1
]}

Nakanishi, Masako ^{[1
]}

Yoshida, Michiko ^{[1
]}

Wakabayashi, Makoto ^{[1
,3
]}

Matsuda, Akio ^{[3
]}

Maeda, Yoshinobu ^{[2
]}

Suzuki, Yutaka ^{[4
]}

Sugano, Sumio ^{[4
]}

Whitson, Robert H. ^{[5
]}

Nishimura, Riko ^{[1
]}

Yoneda, Toshiyuki ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Dent, Dept Mol & Cellular Biochem, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Grad Sch Dent, Dept Prosthodont & Oral Rehabil, Suita, Osaka 5650871, Japan

[3] Asahi Kasei Pharma Corp, Lab Adv Drug, Discovery Pharmaceut Res Ctr, Shizuoka 4102321, Japan

[4] Univ Tokyo, Grad Sch Frontier Sci, Kashiwa, Chiba 2778561, Japan

[5] City Hope Natl Med Ctr, Div Mol Biol, Beckman Res Inst, Duarte, CA 91010 USA

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

关键词：

AUTOSOMAL SEX REVERSAL; CHONDROCYTE DIFFERENTIATION; CAMPOMELIC DYSPLASIA; BINDING-PROTEIN; LONG FORM; SOX9; TRANSCRIPTION; EXPRESSION; GROWTH; ASSOCIATION;

D O I：

10.1038/ncomms3850

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：11

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