Sox10, a novel transcriptional modulator in glial cells

Sox10, a novel transcriptional modulator in glial cells
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DOI:
10.1523/jneurosci.18-01-00237.1998
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发表时间:
1998-01-01
影响因子:
5.3
通讯作者:
Wegner, M
Wegner, M
中科院分区:
医学1区
文献类型:
--
作者:
Kuhlbrodt, K;Herbarth, B;Wegner, M

文献摘要

被引文献

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Sox蛋白的特征在于具有与性别决定因子SRY的高迁移率族结构域相似的DNA结合结构域。在这里,我们报告的Sox 10,一种新的蛋白质,主要表达在神经系统的胶质细胞。在发育过程中,Sox 10首先出现在形成的神经嵴中,并随着这些细胞促进PNS的形成而继续表达,最后分化为雪旺细胞。在中枢神经系统中,Sox 10转录本最初仅限于神经胶质前体细胞,后来在成年脑的少突胶质细胞中检测到。功能研究未能揭示Sox 10的自主转录活性。相反,Sox 10与POU结构域蛋白Tst-1/Oct 6/SCIP协同发挥作用,在雪旺细胞发育的某些阶段与其共表达。协同作用依赖于结合到目标启动子中的相邻位点,由两种蛋白质的N-末端区域介导,并且在Sox 10和其他几种POU结构域蛋白之间不能观察到。有趣的是,Sox 10还调节Pax 3和Krox-20的功能,这两个转录因子参与了雪旺细胞的发育。我们提出了Sox 10在赋予细胞特异性的其他转录因子在发育和成熟的神经胶质细胞的功能的作用。
Sox proteins are characterized by possession of a DNA-binding domain with similarity to the high-mobility group domain of the sex determining factor SRY. Here, we report on Sox10, a novel protein with predominant expression in glial cells of the nervous system. During development Sox10 first appeared in the forming neural crest and continued to be expressed as these cells contributed to the forming PNS and finally differentiated into Schwann cells. In the CNS, Sox10 transcripts were originally confined to glial precursors and later detected in oligodendrocytes of the adult brain. Functional studies failed to reveal autonomous transcriptional activity for Sox10. Instead, Sox10 functioned synergistically with the POU domain protein Tst-1/Oct6/SCIP with which it is coexpressed during certain stages of Schwann cell development. Synergy depended on binding to adjacent sites in target promoters, was mediated by the N-terminal regions of both proteins, and could not be observed between Sox10 and several other POU domain proteins. Interestingly Sox10 also modulated the function of Pax3 and Krox-20, two other transcription factors involved in Schwann cell development. We propose a role for Sox10 in conferring cell specificity to the function of other transcription factors in developing and mature glia.