Understanding the mechanism and function of transposable element expression in early embryonic development

了解早期胚胎发育中转座元件表达的机制和功能

• 批准号: 2735096
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2735096
• 关键词: Understanding; mechanism; function; transposable; element

Around half of the mammalian genome is formed of transposable elements (TEs) or "jumping genes". These unusual elements can replicate and insert additional copies of themselves into distant genomic loci. TE insertion can cause many issues for the host genome, hence most TEs are silenced and not expressed in most cells. Interestingly, TE expression is essential for embryonic development. Using Single CELl LOng-read RNA-sequencing (CELLO-seq), we will characterise locus-specific TE expression in single cells from early mouse embryos. Subsequently, we aim to assess the mechanism by which specific TEs are activated during early development, as well as the function of expressed loci during development. We will curate a database of existing and novel genomic information to characterise the regulatory landscape of mESCs. We will use this data to assess mechanisms of TE transcriptional activation and the roles of specific TEs in gene regulation, which we will functionally validate using enhancer and TE KO cell lines. As TE insertions occur naturally in organisms, we will analyse the impact of TE insertions in human blood lineages, specifically erythroid, using a database of the human regulatory and transcriptional landscape. Overall, this work will identify TE-loci essential for embryonic development. It will help us to identify the rules for TE regulation and to identify roles for specific TE loci as genetic regulators, both in embryos and in differentiated lineages.UKRI-BBSRC priority areas: Understanding the rules of life, transformative technologies

大约一半的哺乳动物基因组由转座因子（TE）或“跳跃基因”组成。这些不寻常的元件可以复制并将其自身的额外拷贝插入到遥远的基因组位点中。TE插入会对宿主基因组造成许多问题，因此大多数TE在大多数细胞中被沉默并且不表达。有趣的是，TE表达对于胚胎发育至关重要。使用单CEL 1长读RNA测序（CELLO-seq），我们将在来自早期小鼠胚胎的单细胞中进行基因座特异性TE表达。随后，我们的目标是评估特定的TE在早期发育过程中被激活的机制，以及发育过程中表达位点的功能。我们将策划一个现有的和新的基因组信息的数据库，以确定mESCs的监管格局。我们将使用这些数据来评估TE转录激活的机制和特定TE在基因调控中的作用，我们将使用增强子和TE KO细胞系对其进行功能验证。由于TE插入在生物体中自然发生，我们将使用人类调控和转录景观的数据库分析TE插入在人类血液谱系，特别是红系中的影响。总的来说，这项工作将确定胚胎发育所必需的TE基因座。它将帮助我们确定TE调控的规则，并确定特定TE基因座在胚胎和分化谱系中作为遗传调控因子的作用。UKRI-BBSRC优先领域：了解生命规则，变革性技术