Activation of a T-box-Otx2-Gsc gene network independent of TBP and TBP-related factors.
Activation of a T-box-Otx2-Gsc gene network independent of TBP and TBP-related factors.
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DOI：
10.1242/dev.127936
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发表时间：
2016-04-15
期刊：
影响因子：
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通讯作者：
Veenstra GJ
中科院分区：
文献类型：
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作者：
Gazdag E;Jacobi UG;van Kruijsbergen I;Weeks DL;Veenstra GJ
胚胎发育依赖于激活和抑制调控影响，这些影响忠实地整合在单个基因的核心启动子上。在脊椎动物中，识别核心启动子的基本机制包括tata结合蛋白（TBP）和两个TBP相关因子。在爪蟾胚胎中，三个TBP家族因子都是发育所必需的，并且是不同基因亚群表达所必需的。在这里，我们报道了一种涉及中胚层和组织者基因表达的非规范TBP家族不敏感（TFI）转录起始机制。通过TBP家族单敲和三敲实验、α-amanitin处理、转录组分析和染色质免疫沉淀，我们发现TFI基因的表达不能用功能冗余来解释，而是由主动转录支持，并显示RNA聚合酶II的启动形式正常募集到启动子。引人注目的是，Gcn5（也称为Kat2a）是一种参与转录起始的共激活因子，当TBP家族因子耗尽时，TFI基因启动子的募集会增加。TFI基因是紧密连接的TBP家族不敏感T-box-Otx2-Gsc相互作用网络的一部分。结果表明，这个由Vegt、Eomes、Otx2和Gsc结合的基因网络利用了一种新颖、灵活和非规范的转录机制，不需要TBP或TBP相关因子。一个胚胎基因网络，其中许多在中胚层和组织者中表达，可以通过非规范机制启动转录。
Embryonic development relies on activating and repressing regulatory influences that are faithfully integrated at the core promoter of individual genes. In vertebrates, the basal machinery recognizing the core promoter includes TATA-binding protein (TBP) and two TBP-related factors. In Xenopus embryos, the three TBP family factors are all essential for development and are required for expression of distinct subsets of genes. Here, we report on a non-canonical TBP family-insensitive (TFI) mechanism of transcription initiation that involves mesoderm and organizer gene expression. Using TBP family single- and triple-knockdown experiments, α-amanitin treatment, transcriptome profiling and chromatin immunoprecipitation, we found that TFI gene expression cannot be explained by functional redundancy, is supported by active transcription and shows normal recruitment of the initiating form of RNA polymerase II to the promoter. Strikingly, recruitment of Gcn5 (also known as Kat2a), a co-activator that has been implicated in transcription initiation, to TFI gene promoters is increased upon depletion of TBP family factors. TFI genes are part of a densely connected TBP family-insensitive T-box-Otx2-Gsc interaction network. The results indicate that this network of genes bound by Vegt, Eomes, Otx2 and Gsc utilizes a novel, flexible and non-canonical mechanism of transcription that does not require TBP or TBP-related factors. Highlighted article: A network of embryonic genes, many of which are expressed in the mesoderm and the organiser, can initiate transcription through a non-canonical mechanism.