RRC ID 61333
Author Hata K, Takashima R, Amano K, Ono K, Nakanishi M, Yoshida M, Wakabayashi M, Matsuda A, Maeda Y, Suzuki Y, Sugano S, Whitson RH, Nishimura R, Yoneda T.
Title Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes.
Journal Nat Commun
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.
Volume 4
Pages 2850
Published 2013-1-1
DOI 10.1038/ncomms3850
PII ncomms3850
PMID 24276541
MeSH Animals Chondrocytes / cytology* Chondrocytes / enzymology Chondrocytes / metabolism Chondrogenesis* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Female Gene Expression Regulation* Histone Demethylases / genetics Histone Demethylases / metabolism* Histones / genetics Histones / metabolism Male Methylation Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Knockout NIH 3T3 Cells Promoter Regions, Genetic Protein Binding SOX9 Transcription Factor / genetics SOX9 Transcription Factor / metabolism* Transcription Factors / genetics Transcription Factors / metabolism*
IF 11.878
Human and Animal Cells ATDC5(RCB0565) 10T1/2(RCB0247)