Dy Peter, Penzo-Méndez Alfredo, Wang Hongzhe, Pedraza Carlos E, Macklin Wendy B, Lefebvre Véronique
Department of Cell Biology and Orthopaedic Research Center Cleveland Clinic, Cleveland, OH, USA.
Nucleic Acids Res. 2008 May;36(9):3101-17. doi: 10.1093/nar/gkn162. Epub 2008 Apr 10.
The group C of Sry-related high-mobility group (HMG) box (Sox) transcription factors has three members in most vertebrates: Sox4, Sox11 and Sox12. Sox4 and Sox11 have key roles in cardiac, neuronal and other major developmental processes, but their molecular roles in many lineages and the roles of Sox12 remain largely unknown. We show here that the three genes are co-expressed at high levels in neuronal and mesenchymal tissues in the developing mouse, and at variable relative levels in many other tissues. The three proteins have conserved remarkable identity through evolution in the HMG box DNA-binding domain and in the C-terminal 33 residues, and we demonstrate that the latter residues constitute their transactivation domain (TAD). Sox11 activates transcription several times more efficiently than Sox4 and up to one order of magnitude more efficiently than Sox12, owing to a more stable alpha-helical structure of its TAD. This domain and acidic domains interfere with DNA binding, Sox11 being most affected and Sox4 least affected. The proteins are nevertheless capable of competing with one another in reporter gene transactivation. We conclude that the three SoxC proteins have conserved overlapping expression patterns and molecular properties, and might therefore act in concert to fulfill essential roles in vivo.
性别决定区Y盒（Sry）相关的高迁移率族（HMG）盒转录因子C组（SoxC）在大多数脊椎动物中包含三个成员：Sox4、Sox11和Sox12。Sox4和Sox11在心脏、神经及其他主要发育过程中发挥关键作用，但它们在许多细胞谱系中的分子作用以及Sox12的作用在很大程度上仍不清楚。我们在此表明，这三个基因在发育中的小鼠的神经和间充质组织中高水平共表达，而在许多其他组织中相对水平各不相同。这三种蛋白质在HMG盒DNA结合结构域以及C末端的33个残基中，通过进化保留了显著的一致性，并且我们证明后者的残基构成了它们的反式激活结构域（TAD）。由于其TAD具有更稳定的α-螺旋结构，Sox11激活转录的效率比Sox4高几倍，比Sox12高一个数量级。该结构域和酸性结构域会干扰DNA结合，其中Sox11受影响最大，Sox4受影响最小。不过，这些蛋白质在报告基因反式激活中能够相互竞争。我们得出结论，这三种SoxC蛋白具有保守的重叠表达模式和分子特性，因此可能协同作用以在体内发挥重要作用。
