SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse
SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse
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DOI：
10.1006/dbio.1996.8487
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发表时间：
1997-03-01
影响因子：
2.7
通讯作者：
Koopman, P
中科院分区：
文献类型：
--
作者：
Ng, LJ;Wheatley, S;Koopman, P
两条证据表明 Sry 相关基因 Sox9 对于哺乳动物胚胎的软骨形成很重要。 Sox9 mRNA 在小鼠软骨形成浓缩物中表达，已知人类 SOX9 的突变会导致骨骼发育不良。我们在此表明，小鼠 SOX9 蛋白能够与 DNA 中的 SOX/SRY 共有基序结合，并包含模块化转录激活结构域，这与 SOX9 作为作用于软骨发育相关基因的转录因子的作用一致。其中一个基因是 Col2a1，它编码 II 型胶原蛋白，这是软骨的主要结构成分。我们详细比较了小鼠发育过程中 Sox9 和 Col2a1 的表达。在软骨形成组织中，这两个基因的表达谱非常相似。在一些非软骨组织（如脊索、耳囊和神经管）中检测到共表达，但在其他组织（如心脏和肺）中这两种基因的表达存在差异。使用 SOX9 特异性抗体进行的免疫组织化学显示，SOX9 蛋白的表达反映了 Sox9 mRNA 的分布。我们的结果表明 SOX9 蛋白参与软骨形成过程中 Col2a1 的调节，但这种调节可能依赖于其他辅助因子。 (C) 1997 年学术出版社。
Two lines of evidence suggest that the Sry-related gene Sox9 is important for chondrogenesis in mammalian embryos. Sox9 mRNA is expressed in chondrogenic condensations in mice, and mutations in human SOX9 are known to cause skeletal dysplasia. We show here that mouse SOX9 protein is able to bind to a SOX/SRY consensus motif in DNA and contains a modular transcriptional activation domain, consistent with a role for SOX9 as a transcription factor acting on genes involved in cartilage development. One such gene is Col2a1, which encodes type II collagen, the major structural component of cartilage. We have compared, in detail, the expression of Sox9 and Col2a1 during mouse development. In chondrogenic tissues the expression profiles of the two genes were remarkably similar. Coexpression was detected in some nonchondrogenic tissues such as the notochord, otic vesicle, and neural tube, but others such as heart and lung differed in their expression of the two genes. Immunohistochemistry using an antibody specific for SOX9 revealed that expression of SOX9 protein mirrored the distribution of Sox9 mRNA. Our results suggest that SOX9 protein is involved in the regulation of Col2a1 during chondrogenesis, but that this regulation is likely to depend on additional cofactors. (C) 1997 Academic Press.