Condensin-driven remodelling of X chromosome topology during dosage compensation

Genome-wide chromosome conformation capture analysis in C. elegans reveals that the dosage compensation complex, a condensin complex, remodels the X chromosomes of hermaphrodites into a sex-specific topology distinct from autosomes while regulating gene expression chromosome-wide. X-chromosome takes shapes Dosage compensation in the roundworm Caenorhabditis elegans is a good model for understanding the role of three-dimensional chromosome organization in regulating gene expression. Here, Barbara Meyer and colleagues use genome-wide chromosome conformation capture techniques in wild-type XX hermaphrodite embryos and those lacking the dosage compensation complex (DCC), to obtain three-dimensional maps of the C. elegans genome. The DCC remodels hermaphrodite X chromosomes into a spatial conformation of topologically associating domains that is distinct from that on autosomes. The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure 1 , 2 . Here we perform genome-wide chromosome conformation capture analysis, fluorescent in situ hybridization (FISH), and RNA-seq to obtain comprehensive three-dimensional (3D) maps of the Caenorhabditis elegans genome and to dissect X chromosome dosage compensation, which balances gene expression between XX hermaphrodites and XO males. The dosage compensation complex (DCC), a condensin complex, binds to both hermaphrodite X chromosomes via sequence-specific recruitment elements on X ( rex sites) to reduce chromosome-wide gene expression by half 3 , 4 , 5 , 6 , 7 . Most DCC condensin subunits also act in other condensin complexes to control the compaction and resolution of all mitotic and meiotic chromosomes 5 , 6 . By comparing chromosome structure in wild-type and DCC-defective embryos, we show that the DCC remodels hermaphrodite X chromosomes into a sex-specific spatial conformation distinct from autosomes. Dosage-compensated X chromosomes consist of self-interacting domains (∼1 Mb) resembling mammalian topologically associating domains (TADs) 8 , 9 . TADs on X chromosomes have stronger boundaries and more regular spacing than on autosomes. Many TAD boundaries on X chromosomes coincide with the highest-affinity rex sites and become diminished or lost in DCC-defective mutants, thereby converting the topology of X to a conformation resembling autosomes. rex sites engage in DCC-depende