Topoisomerases I and II facilitate condensin DC translocation to organize and repress X chromosomes in C. elegans

Summary

Condensin complexes are evolutionarily conserved molecular motors that translocate along DNA and form loops. While condensin-mediated DNA looping is thought to direct the chain-passing activity of topoisomerase II to separate sister chromatids, it is not known if topological constraints in turn regulate loop formation in vivo. Here we applied auxin inducible degradation of topoisomerases I and II to determine how DNA topology affects the translocation of an X chromosome specific condensin that represses transcription for dosage compensation in C. elegans (condensin DC). We found that both topoisomerases colocalize with condensin DC and control its movement at different genomic scales. TOP-2 depletion hindered condensin DC translocation over long distances, resulting in accumulation around its X-specific recruitment sites and shorter Hi-C interactions. In contrast, TOP-1 depletion did not affect long-range spreading but resulted in accumulation of condensin DC within expressed gene bodies. Both TOP-1 and TOP-2 depletions resulted in X chromosome transcriptional upregulation indicating that condensin DC translocation at both scales is required for its function in gene repression. Together the distinct effects of TOP-1 and TOP-2 on condensin DC distribution revealed two distinct modes of condensin DC association with chromatin: long-range translocation that requires decatenation/unknotting of DNA and short-range translocation across genes that requires resolution of transcription-induced supercoiling.