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

Ana Karina Morao, Jun Kim, Daniel Obaji, Siyu Sun, Sevinç Ercan

Research output: Contribution to journalArticlepeer-review

Abstract

Condensins are evolutionarily conserved molecular motors that translocate along DNA and form loops. To address how DNA topology affects condensin translocation, we applied auxin-inducible degradation of topoisomerases I and II and analyzed the binding and function of an interphase condensin that mediates X chromosome dosage compensation in C. elegans. TOP-2 depletion reduced long-range spreading of condensin-DC (dosage compensation) from its recruitment sites and shortened 3D DNA contacts measured by Hi-C. TOP-1 depletion did not affect long-range spreading but resulted in condensin-DC accumulation within expressed gene bodies. Both TOP-1 and TOP-2 depletion resulted in X chromosome derepression, indicating that condensin-DC translocation at both scales is required for its function. Together, the distinct effects of TOP-1 and TOP-2 suggest two distinct modes of condensin-DC association with chromatin: long-range DNA loop extrusion that requires decatenation/unknotting of DNA and short-range translocation across genes that requires resolution of transcription-induced supercoiling.

Original languageEnglish (US)
Pages (from-to)4202-4217.e5
JournalMolecular Cell
Volume82
Issue number22
DOIs
StatePublished - Nov 17 2022

Keywords

  • 3D organization
  • C. elegans
  • condensin
  • loop extrusion
  • SMC complex
  • topoisomerases
  • transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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