Smc3 acetylation, Pds5 and Scc2 control the translocase activity that establishes cohesin dependent chromatin loops

Nathalie Bastié (1) , Christophe Chapard (2) , Lise Dauban (1) , Olivier Gadal (1) , Frederic Beckouet (3, 1) , Romain Koszul (2)

1 MCD - Unité de biologie Moléculaire, Cellulaire et du Développement
2 Régulation spatiale des Génomes - Spatial Regulation of Genomes
3 LBME - Laboratoire de biologie moléculaire eucaryote

ABSTRACT Chromosome spatial organization and dynamics influence DNA-related metabolic processes. SMC complexes like cohesin are essential instruments of chromosome folding. Cohesin-dependent chromatin loops bring together distal loci to regulate gene transcription, DNA repair and V(D)J recombination processes. Here we characterize further the roles of members of the cohesin holocomplex in regulating chromatin loop expansion, showing that Scc2, which stimulates cohesin ATPase activity, is essential for the translocation process required to extend DNA loop length. Eco1-dependent acetylation of Smc3 during S phase counteracts this activity through the stabilization of Pds5, to finely tune loop sizes and stability during G2. Inhibiting Pds5 in G2 leads to a strong enlargement of pre-established, stable DNA loops, in a Scc2-dependent manner. Altogether, the study strongly supports a Scc2-mediated translocation process driving expansion of DNA loops in living cells.

Mots clés: Cohesin; DNA loop extrusion; DNA loop borders; Hi-C metaphase yeast; calibrated ChIP-seq

Domaines: Biochimie, Biologie Moléculaire

Nathalie Bastié, Christophe Chapard, Lise Dauban, Olivier Gadal, Frederic Beckouet, et al.. Smc3 acetylation, Pds5 and Scc2 control the translocase activity that establishes cohesin dependent chromatin loops. 2022. ⟨hal-03454422⟩