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少突胶质细胞中连接蛋白47的表达受Sox10转录因子调控。

Expression of connexin47 in oligodendrocytes is regulated by the Sox10 transcription factor.

作者信息

Schlierf Beate, Werner Torsten, Glaser Gabi, Wegner Michael

机构信息

Institut für Biochemie, Universität Erlangen-Nürnberg, Germany.

出版信息

J Mol Biol. 2006 Aug 4;361(1):11-21. doi: 10.1016/j.jmb.2006.05.072. Epub 2006 Jun 15.

Abstract

In the central nervous system, Connexin32 and Connexin47 are confined to oligodendrocytes where they contribute to myelin formation and maintenance, and are essential for establishing a functional glial syncytium that ensures ionic homeostasis. Despite their importance, not much is known about the regulation of connexin gene expression in oligodendrocytes. Here, we identify group E Sox proteins, in particular Sox10, as essential transcriptional regulators of both connexins. Not only was expression of Connexin32 and Connexin47 severely compromised in spinal cords of mouse mutants with reduced amounts of group E Sox proteins. Sox10 also stimulated in transient transfections the Connexin32 promoter as well as Connexin47 promoter 1b which is the main Connexin47 promoter active in the postnatal spinal cord. Detailed characterization of Connexin47 promoter 1b identified a single monomer binding site that mediated Sox10-dependent promoter activation. The region containing this binding site was also occupied by endogenous Sox10 in 33B oligodendroglioma cells. These results add Connexin47 and Connexin32 to the list of Sox10 target genes and argue that Sox10 may influence transcription of many terminal differentiation and myelination genes in oligodendrocytes as an essential regulatory component of the myelination program.

摘要

在中枢神经系统中,连接蛋白32(Connexin32)和连接蛋白47(Connexin47)局限于少突胶质细胞,它们在髓鞘形成和维持过程中发挥作用,对于建立确保离子稳态的功能性胶质细胞合体至关重要。尽管它们很重要,但关于少突胶质细胞中连接蛋白基因表达的调控却知之甚少。在此,我们确定E组Sox蛋白,特别是Sox10,是这两种连接蛋白的关键转录调节因子。不仅在E组Sox蛋白数量减少的小鼠突变体脊髓中,连接蛋白32和连接蛋白47的表达严重受损。Sox10在瞬时转染中还刺激了连接蛋白32启动子以及连接蛋白47启动子1b,后者是出生后脊髓中活跃的主要连接蛋白47启动子。对连接蛋白47启动子1b的详细表征确定了一个介导Sox10依赖性启动子激活的单体结合位点。在33B少突胶质细胞瘤细胞中,含有该结合位点的区域也被内源性Sox10占据。这些结果将连接蛋白47和连接蛋白32添加到Sox10靶基因列表中,并表明Sox10作为髓鞘形成程序的重要调节成分,可能影响少突胶质细胞中许多终末分化和髓鞘形成基因的转录。

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