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Dynamic regulation of the transcription initiation landscape at single nucleotide resolution during vertebrate embryogenesis

机译:在脊椎动物胚胎发生过程中以单核苷酸分辨率动态调节转录起始态。

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摘要

textabstractSpatiotemporal control of gene expression is central to animal development. Core promoters represent a previously unanticipated regulatory level by interacting with cis-regulatory elements and transcription initiation in different physiological and developmental contexts. Here, we provide a first and comprehensive description of the core promoter repertoire and its dynamic use during the development of a vertebrate embryo. By using cap analysis of gene expression (CAGE), we mapped transcription initiation events at single nucleotide resolution across 12 stages of zebrafish development. These CAGE-based transcriptome maps reveal genome-wide rules of core promoter usage, structure, and dynamics, key to understanding the control of gene regulation during vertebrate ontogeny. They revealed the existence of multiple classes of pervasive intra- and intergenic post-transcriptionally processed RNA products and their developmental dynamics. Among these RNAs, we report splice donor site-associated intronicRNA(sRNA) to be specific to genes of the splicing machinery. For the identification of conserved features, we compared the zebrafish data sets to the first CAGE promoter map of Tetraodon and the existing human CAGE data. We show that a number of features, such as promoter type, newly discovered promoter properties such as a specialized purine-rich initiator motif, as well as sRNAs and the genes in which they are detected, are conserved in mammalian and Tetraodon CAGE-defined promoter maps. The zebrafish developmental promoterome represents a powerful resource for studying developmental gene regulation and revealing promoter features shared across vertebrates.
机译:textabstract基因表达的时空控制对于动物发育至关重要。核心启动子通过在不同的生理和发育环境下与顺式调节元件相互作用和转录起始来代表以前未曾预料到的调节水平。在这里,我们提供了核心启动子库及其在脊椎动物胚胎发育过程中动态使用的第一个全面描述。通过使用基因表达的上限分析(CAGE),我们在斑马鱼发育的12个阶段以单核苷酸分辨率绘制了转录起始事件。这些基于CAGE的转录组图谱揭示了核心启动子使用,结构和动力学的全基因组规则,这是了解脊椎动物个体发育过程中基因调控控制的关键。他们揭示了存在多种类型的普遍的基因内和基因间转录后加工的RNA产物及其发育动力学。在这些RNA中,我们报告了剪接供体位点相关的intronicRNA(sRNA)特异于剪接机制的基因。为了识别保守特征,我们将斑马鱼数据集与四角形龙的第一个CAGE启动子图和现有的人类CAGE数据进行了比较。我们显示了许多功能,例如启动子类型,新发现的启动子特性(例如专门的富含嘌呤的启动子基序)以及sRNA和其中检测到它们的基因在哺乳动物和四角形龙笼定义的启动子中是保守的地图。斑马鱼发育促进子是研究发育基因调控和揭示整个脊椎动物共有的启动子特征的有力资源。

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