Transposable elements, their controllers and the genesis of human-specific transcriptional networks
|Title||Transposable elements, their controllers and the genesis of human-specific transcriptional networks|
|Sponsor||European Research Council - Advanced Grant (ERC-AdG)|
Transposable elements (TEs) account for more than two thirds of the human genome. They can inactivate genes, provide novel coding functions, sprinkle chromosomes with recombination-prone repetitive sequences, and modulate cellular gene expression through a wide variety of transcriptional and post-transcriptional influences. As a consequence, TEs are considered as essential motors of evolution yet they are occasionally associated with disease, causing about one hundred Mendelian disorders and possibly contributing to several human cancers. As expected for such genomic threats, TEs are subjected to tight epigenetic control imposed from the very first days of embryogenesis, in part owing to their recognition by sequence-specific RNA- and protein-based repressors. It is generally considered that the evolutionary selection of these TE controllers reflects a simple host-pathogen arms race, and that their action results in the early and permanent silencing of their targets. We have recently uncovered new evolutionary evidence and obtained genomic and functional data that invalidate this dual assumption, and suggest instead that transposable elements and their epigenetic controllers establish species-specific transcriptional networks that play critical roles in human development and physiology. The general objective of the present proposal is to explore the breadth of this phenomenon, to decipher its mechanisms, to unveil its functional implications, and to probe how this knowledge could be exploited for basic research, biotechnology and clinical medicine.