Deciphering the roles of transposable elements in 3D genome architecture and gene expression

Title Deciphering the roles of transposable elements in 3D genome architecture and gene expression
Acronym TE-ENHANCERs
Website http://tronolab.epfl.ch
Start date 2016-01-01
End date 2019-12-31
Sponsor Marie Skłodowska-Curie Action (MSCA)

Associated cell lines

Project Description

Establishing and maintaining the pluripotency of embryonic stem cells and controlling their lineage commitment is critical for the development and homeostasis of higher organisms. Key to this process is the influence of DNA regulatory sequences such as promoters, enhancers and insulators, many of which reside in transposable elements (TEs). TEs display exquisitely specific patterns of expression both during development and in adult tissues, and their deregulation has been observed in human diseases, for instance some cancers and neurological disorders. However the knowledge of their involvement in gene regulation and the extend of their impact in development and homeostasis is still rudimental. One model system is the human Embryonic Stem Cell (hESC) which represent a highly interesting system for studying the influence of TEs on transcriptional networks, because in these cells TEs are particularly active, partake to the maintenance of pluripotency and are subjected to highly dynamic control. Accordingly, I will use hESC as a paradigm to study the impact of TEs on the regulation of gene expression. I propose to tackle two major questions during my postdoc: (i) how TEs influence transcription in hESCs, and (ii) how TEs more broadly contribute to the establishment of human-specific gene regulatory networks. Those immediate aims will raise a solid basis for the understanding of their potential roles in pathological conditions.