Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Physiol Res. 2011;60(Suppl 1):S83-91. doi: 10.33549/physiolres.932184. Epub 2011 Jul 19.
Sox3/SOX3 gene is considered to be one of the earliest neural markers in vertebrates. Despite the mounting evidence that Sox3/SOX3 is one of the key players in the development of the nervous system, limited data are available regarding the transcriptional regulation of its expression. This review is focused on the retinoic acid induced regulation of SOX3 gene expression, with particular emphasis on the involvement of retinoid receptors. Experiments with human embryonal carcinoma cells identified two response elements involved in retinoic acid/retinoid X receptor-dependent activation of the SOX3 gene expression: distal atypical retinoic acid-response element, consisting of two unique G-rich boxes separated by 49 bp, and proximal element comprising DR-3-like motif, composed of two imperfect hexameric half-sites. Importantly, the retinoic acid-induced SOX3 gene expression could be significantly down-regulated by a synthetic antagonist of retinoid receptors. This cell model provides a solid base for further studies on mechanism(s) underlying regulation of expression of SOX3 gene, which could improve the understanding of molecular signals that induce neurogenesis in the stem/progenitor cells both during development and in adulthood.
Sox3/SOX3 基因被认为是脊椎动物最早的神经标记物之一。尽管越来越多的证据表明 Sox3/SOX3 是神经系统发育的关键因子之一，但关于其表达的转录调控的信息有限。这篇综述主要集中在视黄酸诱导 Sox3 基因表达的调控上，特别强调了视黄酸受体的参与。用人类胚胎癌细胞进行的实验确定了两个与视黄酸/视黄酸 X 受体依赖性 Sox3 基因表达激活相关的反应元件：由两个独特的富含 G 的盒组成的远端非典型视黄酸反应元件，间隔 49 个碱基；包含 DR-3 样基序的近端元件，由两个不完全的六聚体半位点组成。重要的是，视黄酸诱导的 Sox3 基因表达可以被视黄酸受体的合成拮抗剂显著下调。该细胞模型为进一步研究 Sox3 基因表达调控的机制提供了坚实的基础，这可能有助于理解在发育和成年过程中诱导干细胞/祖细胞神经发生的分子信号。
