Werner Torsten, Hammer Alexander, Wahlbuhl Mandy, Bösl Michael R, Wegner Michael
Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, Erlangen and Max-Planck-Institut für Neurobiologie, Martinsried, Germany.
Nucleic Acids Res. 2007;35(19):6526-38. doi: 10.1093/nar/gkm727. Epub 2007 Sep 26.
Expression and function of the transcription factor Sox10 is predominant in neural crest cells, its derivatives and in oligodendrocytes. To understand how Sox10 expression is regulated during development, we analysed the potential of evolutionary conserved non-coding sequences in the Sox10 genomic region to function as enhancers. By linking these sequences to a beta-galactosidase marker gene under the control of a minimal promoter, five regulatory regions were identified that direct marker gene expression in transgenic mice to Sox10 expressing cell types and tissues in a defined temporal pattern. These possible enhancers of the Sox10 gene mediate Sox10 expression in the otic vesicle, in oligodendrocytes and in several neural crest derivatives including the developing peripheral nervous system and the adrenal gland. They furthermore exhibit overlapping activities and share binding sites for Sox, Lef/Tcf, Pax and AP2 transcription factors. This may explain high level and robustness of Sox10 expression during embryonic development.
转录因子Sox10的表达及功能在神经嵴细胞、其衍生物以及少突胶质细胞中占主导地位。为了解Sox10在发育过程中的表达是如何调控的,我们分析了Sox10基因组区域中进化保守的非编码序列作为增强子的潜力。通过将这些序列与最小启动子控制下的β-半乳糖苷酶标记基因相连,鉴定出了五个调控区域,它们在转基因小鼠中以特定的时间模式将标记基因表达导向表达Sox10的细胞类型和组织。Sox10基因的这些可能的增强子介导了Sox10在耳泡、少突胶质细胞以及包括发育中的外周神经系统和肾上腺在内的几种神经嵴衍生物中的表达。它们还表现出重叠的活性,并共享Sox、Lef/Tcf、Pax和AP2转录因子的结合位点。这可能解释了胚胎发育过程中Sox10表达的高水平和稳健性。