Role of Sox9 transcriptional network during chondrocyte differentiation

Sox9是一种对软骨内成骨至关重要的转录因子；然而，其表观遗传调控的证据仍然难以捉摸。在这里，我们发现ARID5B(富含AT的交互结构域5b)是Sox9的一个新的转录辅助调节因子。ARID5B与Sox9在物理上相互作用，并通过与Col2a1基因启动子的直接结合协同促进软骨形成。ARID5B^-/-小鼠表现出生长迟缓和软骨形成延迟。在ARID5B~-/-软骨细胞中，软骨标志物基因启动子中H3K9的甲基化水平显著升高。总之，我们的发现建立了一个新的骨骼发育的表观基因组机制，其中ARID5B通过促进Sox9和Phf2介导组蛋白去甲基化软骨基因启动子之间的关系来促进软骨形成。

Sox9 is a transcription factor critical for endochondral ossification; however, proof of its epigenetic regulation remains elusive. Here, we identified Arid5b (AT-rich interactive domain 5b) as a novel transcriptional co-regulator for Sox9. Arid5b physically interacted with Sox9 and cooperatively promoted chondrogenesis through direct binding to the Col2a1gene promoter. Arid5b^-/-mice showed growth retardation with delayed chondrogenesis. The methylation level of H3K9 in chondrogenic marker gene promoters was markedly increased in Arid5b^-/- chondrocytes. In conclusion, our findings establish a novel epigenomic mechanism of skeletal development, where Arid5b promotes chondrogenesis by facilitating a relationship between Sox9 and Phf2-mediated histone demethylation of chondrogenic gene promoters.