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

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