Supervised by Jérôme D. Robin

Telomeres are nucleoprotein complexes located at the ends of chromosomes. In Human, telomeres consist of a _T2AG3 repeated motif that shortens with each cell division throughout lifespan. Critically short telomeres lose their protective function and lead to cells senescence, apoptosis or early stages of cancer. Additionally, as telomeres shorten, changes in gene expression and epigenetic equilibrium are triggered in two ways: Telomere Position Effect (TPE) and Telomere Position Effect Over Long Distances (TPE-OLD). TPE is defined by the spreading of suppressive epigenetic marks over proximal genes whereas TPE-OLD is a phenomenon modulating transcription through 3D chromatin structure involving telomere sequences (DNA loops). We aimed to define TPE-OLD mechanisms and its implication in rare diseases. In order to achieve this, we developed two methods based on long read nanopore sequencing. The first one focuses on the establishment of telomere length on specific chromosomes, while at the same time identifying the methylation status of the subtelomere region (TPE analysis). The second method uses chromatin conformation capture techinques to visualize global TPE-OLD interactions. Altogether, our work holds the potential to reveal novel implication of telomeres in human pathologies.

Supervised by Igor Medyna