Dehm Verena, Aberle Tim, Bladé Laura Guerrero, Aprato Jessica, Weider Matthias, Sticht Heinrich, Sock Elisabeth, Wegner Michael
Institut für Biochemie, Friedrich-Alexander-Universität Erlangen-Nürnberg, D91054 Erlangen, Germany.
Zahnklinik3-Kieferorthopädie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, D91054 Erlangen, Germany.
Int J Mol Sci. 2024 Dec 13;25(24):13395. doi: 10.3390/ijms252413395.
Oligodendroglial cells generate myelin sheaths in the vertebrate central nervous system to render rapid saltatory conduction possible and express the highly related Sox8, Sox9 and Sox10 transcription factors. While Sox9 and Sox10 fulfill crucial regulatory roles, Sox8 has only a limited impact on oligodendroglial development and myelination. By replacing Sox10 with Sox8 or Sox9 in the oligodendroglial Oln93 cell line, and comparing the expression profiles, we show here that Sox8 regulates the same processes as Sox10 and Sox9, but exhibits a substantially lower transcriptional activity under standard culture conditions. Sox8 influences fewer genes in their expression and changes their expression level less drastically, despite comparable binding to relevant regulatory regions in oligodendroglial cells. Therefore, it is likely that Sox8 and Sox10 vary in their transcriptional activity because of differences in their interactions with partner proteins. Intriguingly, it is the aminoterminal one third of the Sox protein that is responsible for the differential activities of Sox8 and Sox10, rather than the carboxyterminal two thirds that contain the known transactivation domains. Our study aims to provide an understanding of the relationship of Sox8 and Sox10 as paralogous transcription factors and their degree of functional redundancy in oligodendroglial cells, along with implications for health and disease.
少突胶质细胞在脊椎动物中枢神经系统中生成髓鞘，以使快速跳跃式传导成为可能，并表达高度相关的Sox8、Sox9和Sox10转录因子。虽然Sox9和Sox10发挥着关键的调节作用，但Sox8对少突胶质细胞发育和髓鞘形成的影响有限。通过在少突胶质细胞系Oln93中用Sox8或Sox9替代Sox10，并比较表达谱，我们在此表明Sox8与Sox10和Sox9调节相同的过程，但在标准培养条件下表现出显著较低的转录活性。尽管Sox8与少突胶质细胞中的相关调控区域有类似的结合，但它影响表达的基因较少，且对其表达水平的改变也较小。因此，Sox8和Sox10的转录活性可能因其与伴侣蛋白相互作用的差异而有所不同。有趣的是，负责Sox8和Sox10不同活性的是Sox蛋白的氨基末端三分之一，而不是包含已知反式激活结构域的羧基末端三分之二。我们的研究旨在了解作为旁系同源转录因子的Sox8和Sox10之间的关系，以及它们在少突胶质细胞中的功能冗余程度，以及对健康和疾病的影响。
