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

大约一半的哺乳动物基因组是由转座因子（te）或“跳跃基因”组成的。这些不寻常的元素可以复制并将自己的额外副本插入到遥远的基因组位点中。TE的插入会对宿主基因组造成许多问题，因此大多数TE在大多数细胞中沉默且不表达。有趣的是，TE的表达对胚胎发育至关重要。使用单细胞长读rna测序（CELLO-seq），我们将在早期小鼠胚胎的单细胞中表征位点特异性TE表达。随后，我们的目标是评估特异性te在早期发育过程中被激活的机制，以及在发育过程中表达位点的功能。我们将建立一个现有的和新的基因组信息数据库，以描述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，我们将使用人类调节和转录景观数据库分析TE插入对人类血液谱系，特别是红系的影响。总的来说，这项工作将确定te位点对胚胎发育至关重要。这将有助于我们确定TE调控的规则，并确定在胚胎和分化谱系中特定TE位点作为遗传调控因子的作用。UKRI-BBSRC优先领域：理解生命规则，变革技术

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