Dessynle

Cohesin is a conserved ring-shaped complex that belongs to the Structural Maintenance Complex (SMC) family. In addition to confer sister chromatid cohesion, cohesin has the ability to bridge distant intrachromosomal loci in most genomes. These cis contacts result in the establishment of large chromatin loops along mammalian interphase chromosome, whose roles in processes such as transcription, DNA replication and repair are actively investigated. We and others recently showed that cohesin also organizes yeast mitotic chromosomes into loops, through regulatory pathways similar to those found in mammalian cells. The molecular mechanisms that regulate the formation of loops are actively investigated. Cohesin are proposed to capture small chromatin loops and gradually enlarging them through an active translocation process, until encountering physical roadblocks along the DNA or being spontaneously released. This “loop extrusion” model can lead up to megabase sized structures. Biochemical experiments gave strong support to this model by showing that purified cohesins can indeed extrudes DNA loop. The molecular mechanisms and sequence determinants controlling the establishment, expansion, position and maintenance of these loops in living cells remain actively investigated. Notably, how cohesin cope with the diversity of complex chromatin templates, including the influence of heterochromatin and transcription, on the extrusion process. The project Dessynle aims at mobilizing a set of complementary expertise to investigate these determinants. To reach its goals, it requires the combination of genetics and cutting-edge experimental and computational techniques such synthetic genomics, Hi-C, live microscopy and deep learning, all mastered by the different partners. It will allow us to decipher the determinants of cohesin mediated chromosome folding. Given the ubiquitous nature of cohesin regulation, these results will inspire or drive research in other species as well.