Centre de Recherche des Cordeliers, INSERM UMR S872, 15, Rue de L'Ecole de Médecine, 75006, Paris, France.
J Mol Neurosci. 2012 Feb;46(2):315-23. doi: 10.1007/s12031-011-9585-4. Epub 2011 Jun 24.
Foxn4, a member of the N-family forkhead transcription factors, controls fate decision in mouse retina and spinal cord as well as in zebrafish heart. Analysis of Foxn4 amino acid sequence revealed the presence of a region homologous to the activation domain of its close relative Foxn1 in between C-terminal amino acids 402 and 455 of Foxn4 protein. The requirement of Foxn4 putative activation domain remains to be elucidated. Using a gain-of function approach in rat and chick retinal explants, we report that deletion of Foxn4 putative activation domain results in a complete loss of its activity during retinogenesis. Target promoter transcription assay indicates that this domain is critical for Foxn4 transcriptional regulatory properties in vitro. Accordingly, in chick retinal explants, this domain is required for proper regulation of target retinogenic factors expression by Foxn4. Thus, our study demonstrates that the domain between amino acids 402 and 455 is necessary for Foxn4 transcriptional activity both in vitro and in the retina.
叉头框转录因子 N 家族的 Foxn4 成员控制着小鼠视网膜和脊髓以及斑马鱼心脏的命运决定。对 Foxn4 氨基酸序列的分析表明，在 Foxn4 蛋白的 C 末端氨基酸 402 和 455 之间存在与近亲 Foxn1 的激活结构域同源的区域。Foxn4 假定激活结构域的需求仍有待阐明。我们在大鼠和鸡视网膜外植体中使用功能获得方法，报告称 Foxn4 假定激活结构域的缺失导致其在视网膜发生过程中完全丧失活性。靶启动子转录测定表明，该结构域对于 Foxn4 在体外的转录调控特性至关重要。因此，在鸡视网膜外植体中，该结构域对于 Foxn4 对靶视网膜发生因子表达的适当调节是必需的。因此，我们的研究表明，该结构域在体外和视网膜中对于 Foxn4 的转录活性都是必需的。
