Understanding how condensin folds chromatinized genomes into loops – Condensinchromatin

A major principle of the functional architecture of eukaryotic genomes is their folding into loops of chromatin by DNA-translocases of the SMC family. In vitro studies have shown that SMC complexes binds naked DNA and form of loops of DNA of increasing size through an as yet enigmatic ATP-dependent allosteric reaction called loop extrusion. In vivo, eukaryotic genomes are packed into arrays of nucleosomes that reduce accessibility to DNA for non-histone DNA binding factors, such as SMC. Yet, we still ignore whether and how SMC complexes achieve loop extrusion in vivo, when nucleosome arrays potentially hinder their access to genomic DNA. Condensin is the SMC DNA-translocase that drives the re-organisation of chromatin into mitotic chromosomes in preparation of the genome segregation during anaphase. We have collected robust data indicating that nucleosomes hinder condensin in vivo. We also identified a conserved chromatin-modifying factor that allows condensin to overcome the nucleosome barrier in order to make the chromatin loops that shape mitotic chromosomes. This project aims at further deciphering the interplays between condensin, nucleosomes and this chromatin regulator in order to better determine whether and how nucleosome dynamics underlies condensin’s loop extrusion activity, and chromosome assembly, in vivo.