A conserved mechanism for targeted cohesin loading organises specialised chromosomal domains

Abstract

Cohesin organises chromosomes through loop extrusion, yet how cohesin loading is targeted to specific genomic regions to shape chromosome architecture remains poorly understood. Here, we identify a conserved mechanism that directs cohesin loading to specialised chromosomal domains in Schizosaccharomyces pombe. Mutation of a conserved interaction surface in the cohesin loader Scc4/Ssl3 abolishes cohesin enrichment at centromeres and ribosomal DNA while largely preserving cohesin levels along chromosome arms, demonstrating that domain-specific accumulation depends on targeted recruitment rather than global loading capacity. We further identify the nucleolar protein Dnt1 as a receptor for cohesin loading at rDNA and show that it is required for proper organisation of this domain. High-resolution MicroC-XL maps reveal that targeted cohesin loading positions loop-based interactions within pericentromeres and rDNA without disrupting larger-scale domain boundaries. Together, these findings show that domain-specific receptors acting through a conserved loader interface direct cohesin positioning and identify targeted loading as a conserved organising principle for specialised chromosomal domains.