The three SoxC proteins--Sox4, Sox11 and Sox12--exhibit overlapping expression patterns and molecular properties.

The three SoxC proteins--Sox4, Sox11 and Sox12--exhibit overlapping expression patterns and molecular properties.
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DOI:
10.1093/nar/gkn162
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发表时间:
2008-05
影响因子:
14.9
通讯作者:
Lefebvre V
Lefebvre V
中科院分区:
生物学2区
文献类型:
--
作者:
Dy P;Penzo-Méndez A;Wang H;Pedraza CE;Macklin WB;Lefebvre V

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在大多数脊椎动物中,Sry 相关高迁移率组 (HMG) 盒 (Sox) 转录因子 C 组有 3 个成员:Sox4、Sox11 和 Sox12。 Sox4 和 Sox11 在心脏、神经元和其他主要发育过程中具有关键作用,但它们在许多谱系中的分子作用以及 Sox12 的作用仍然很大程度上未知。我们在这里表明,这三个基因在发育中的小鼠的神经元和间质组织中以高水平共表达,并且在许多其他组织中以不同的相对水平共表达。通过进化,这三种蛋白在 HMG 盒 DNA 结合域和 C 端 33 个残基中保留了显着的同一性,我们证明后面的残基构成了它们的反式激活域 (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 高数倍,比 Sox12 高一个数量级。该结构域和酸性结构域会干扰 DNA 结合,Sox11 受影响最大,Sox4 受影响最小。然而,这些蛋白质能够在报告基因反式激活方面相互竞争。我们得出的结论是,三种 SoxC 蛋白保留了重叠的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。
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 α-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.
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