Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Hokkaido 060-0814, Japan.
Gene. 2012 Jan 10;491(2):232-6. doi: 10.1016/j.gene.2011.09.007. Epub 2011 Sep 22.
Brachyury, a member of the T-box transcription family, has been suggested to be essential for morphogenetic movements in various processes of animal development. However, little is known about its critical transcriptional targets. In order to identify targets of Brachyury and understand the molecular mechanisms underlying morphogenetic movements, we first searched the genome sequence of Xenopus tropicalis, the only amphibian genomic sequence available, for Brachyury-binding sequences known as T-half sites, and then screened for the ones conserved between vertebrate genomes. We found three genes that have evolutionarily conserved T-half sites in the promoter regions and examined these genes experimentally to determine whether their expressions were regulated by Brachyury, using the animal cap system of Xenopus laevis embryos. Eventually, we obtained evidence that vimentin, encoding an intermediate filament protein, was a potential target of Brachyury. This is the first report to demonstrate that Brachyury might affect the cytoskeletal structure through regulating the expression of an intermediate filament protein, vimentin.
Brachyury 是 T 盒转录因子家族的成员，被认为在动物发育的各种形态发生过程中对于形态发生运动至关重要。然而，关于其关键的转录靶标知之甚少。为了鉴定 Brachyury 的靶标并了解形态发生运动背后的分子机制，我们首先在唯一可用的两栖动物基因组序列——非洲爪蟾（Xenopus tropicalis）的基因组序列中搜索了已知的 Brachyury 结合序列，即 T 半位点，然后筛选了脊椎动物基因组中保守的 T 半位点。我们在启动子区域发现了三个具有进化保守 T 半位点的基因，并使用非洲爪蟾（Xenopus laevis）胚胎的动物帽系统进行实验，检查这些基因的表达是否受 Brachyury 调控。最终，我们获得了证据表明，编码中间丝蛋白的波形蛋白（vimentin）是 Brachyury 的一个潜在靶标。这是第一项表明 Brachyury 可能通过调节中间丝蛋白波形蛋白（vimentin）的表达来影响细胞骨架结构的报告。
