Structural Basis of Condensin Recruitment for X Chromosome Repression

Valdes, A.; Amudhan, G.; Bernasconi, D.; Erkan, S.; Hassler, M.; Suter, I.; Wilde, B.; Bender, J.; Warscheid, B.; Meister, P.; Haering, C. H.

doi:10.64898/2026.03.13.711519

bioRxiv · 10.64898/2026.03.13.711519

Structural Basis of Condensin Recruitment for X Chromosome Repression

Valdes, A.·Amudhan, G.·Bernasconi, D.·Erkan, S.·Hassler, M.·Suter, I.·Wilde, B.·Bender, J.·Warscheid, B.·Meister, P.·Haering, C. H.

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Abstract

In Caenorhabditis elegans, the condensin IDC complex represses transcription from both X chromosomes in hermaphrodites to achieve dosage compensation. How condensin IDC is specifically recruited to the X chromosomes in coordination with sex determination and dosage compensation (SDC) proteins and how it modulates gene expression have, however, remained unresolved. Here, we identify SDC-3 as the key adaptor that directly binds the elbow coiled-coil domain of the condensin IDC-specific SMC subunit DPY-27. Using cryo-electron microscopy, we determine the structure of the SDC-3 adaptor domain bound to an auto-inhibited condensin IDC holoenzyme. Disrupting this interaction compromises dosage compensation and diminishes condensin IDC enrichment on the X chromosomes. Upon overcoming auto-inhibition, condensin IDC exhibits robust DNA loop-extrusion activity comparable to that of canonical condensin. We propose that SDC-3-anchored condensin IDC exploits loop-extrusion to reorganize X-chromosome chromatin and mediate chromosome-wide transcriptional repression.

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Valdes, A., Amudhan, G., Bernasconi, D., Erkan, S., Hassler, M., Suter, I., Wilde, B., Bender, J., Warscheid, B., Meister, P., Haering, C. H.. 2026-03-15. Structural Basis of Condensin Recruitment for X Chromosome Repression. https://doi.org/10.64898/2026.03.13.711519

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