Control of myelination in Schwann cells:: a Krox20 cis-regulatory element integrates Oct6, Brn2 and Sox10 activities
Control of myelination in Schwann cells:: a Krox20 cis-regulatory element integrates Oct6, Brn2 and Sox10 activities
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DOI：
10.1038/sj.embor.7400573
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发表时间：
2006-01-01
期刊：
影响因子：
7.7
通讯作者：
Charnay, P
中科院分区：
文献类型：
--
作者：
Ghislain, J;Charnay, P
雪旺细胞的髓鞘形成受多种转录因子控制，包括POU蛋白Oct6和Brn2、高迁移率基团蛋白Sox10和锌指蛋白Krox20。这些因素的功能如何在髓鞘形成的控制中整合还没有确定。之前，我们在雪旺细胞髓鞘形成过程中发现了一个控制Krox20表达的增强元件。本文将细胞培养实验与转基因相结合，鉴定直接作用于Krox20上游的转录因子。结果表明，在早髓鞘-髓鞘过渡过程中，作用于该增强子的Oct6和Brn2直接激活了Krox20的表达。此外，这些POU蛋白与Sox10之间的增强子依赖性协同作用表明，Krox20的表达需要这些因子的组合。这些结果解决了之前关于Oct6和Brn2在髓鞘形成过程中的作用机制的争议，并为Waardenberg-Hirschsprung病患者髓鞘缺乏（即Sox10突变可能导致Krox20表达缺失）提供了解释。
Myelination in Schwann cells is governed by several transcription factors, including the POU proteins Oct6 and Brn2, the high mobility group protein Sox10 and the zinc-finger protein Krox20. How the function of these factors is integrated in the control of myelination has not been established. Previously, we identified an enhancer element controlling Krox20 expression throughout myelination in Schwann cells. In this paper, cell culture experiments were combined with transgenesis to identify transcription factors acting directly upstream of Krox20. The results show that during the promyelin-myelin transition, Krox20 expression is directly activated by Oct6 and Brn2 acting on this enhancer. In addition, the enhancer-dependent synergism between these POU proteins and Sox10 suggests that Krox20 expression requires this combination of factors. These results resolve previous controversy concerning the mechanism of action of Oct6 and Brn2 during myelination and provide an explanation for myelin deficiencies in Waardenberg-Hirschsprung disease patients whereby Sox10 mutations could lead to a loss of Krox20 expression.