Sox10 Cooperates with the Mediator Subunit 12 during Terminal Differentiation of Myelinating Glia
Sox10 Cooperates with the Mediator Subunit 12 during Terminal Differentiation of Myelinating Glia
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DOI：
10.1523/jneurosci.5178-12.2013
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发表时间：
2013-04
期刊：
影响因子：
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通讯作者：
M. R. Vogl;Simone Reiprich;Melanie Küspert;Thomas Kosian;H. Schrewe;K. Nave;M. Wegner
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文献类型：
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作者：
M. R. Vogl;Simone Reiprich;Melanie Küspert;Thomas Kosian;H. Schrewe;K. Nave;M. Wegner
几个转录因子是必不可少的终末分化的髓鞘神经胶质细胞，其中的高迁移率组域包含蛋白Sox 10。为了更好地了解这些因素如何发挥其作用和形状胶质细胞的表达程序，我们确定并表征了Sox 10和Med 12亚基的调解人复合物，作为一个保守的多蛋白质之间的中间相转录因子和一般的转录机器之间的物理和功能的联系。我们发现，Sox 10的两个保守结构域的Med 12和它的近亲，Med 12-like的C-末端区域绑定。与Med 12样相反，在雪旺细胞和少突胶质细胞中检测到大量的Med 12。其在小鼠中的条件性胶质细胞特异性缺失导致末端分化缺陷，这与Sox 10缺失后获得的缺陷非常相似。在支持的功能合作，这两种蛋白质共同需要Krox 20的诱导和物理相关的关键调控区的Krox 20基因在髓鞘雪旺细胞。我们的结论是，Sox 10的功能在终末分化的髓鞘神经胶质细胞，至少部分由Med 12依赖的招聘的调解人复合物。
Several transcription factors are essential for terminal differentiation of myelinating glia, among them the high-mobility-group-domain-containing protein Sox10. To better understand how these factors exert their effects and shape glial expression programs, we identified and characterized a physical and functional link between Sox10 and the Med12 subunit of the Mediator complex that serves as a conserved multiprotein interphase between transcription factors and the general transcription machinery. We found that Sox10 bound with two of its conserved domains to the C-terminal region of Med12 and its close relative, Med12-like. In contrast to Med12-like, substantial amounts of Med12 were detected in both Schwann cells and oligodendrocytes. Its conditional glia-specific deletion in mice led to terminal differentiation defects that were highly reminiscent of those obtained after Sox10 deletion. In support of a functional cooperation, both proteins were jointly required for Krox20 induction and were physically associated with the critical regulatory region of the Krox20 gene in myelinating Schwann cells. We conclude that Sox10 functions during terminal differentiation of myelinating glia, at least in part by Med12-dependent recruitment of the Mediator complex.