Genome editing of marsupial RSX reveals conserved and divergent principles in mammalian X-inactivation

Authors

Courtois, A., Menchero, S., Ogushi, S., Varsally, W., Wood, S., Decarpentrie, F., Yoshimi, R., Shiraishi, A., Inoue, K., Abe, T., VandeBerg, J. L., Snell, D. M., Kiyonari, H., Turner, J. M. A.

Abstract

X-chromosome inactivation balances X-gene dosage between the sexes in eutherians and marsupials. The lncRNA Xist mediates X-inactivation in eutherians but is absent from marsupials. An evolutionarily unrelated lncRNA, RSX, has been identified in marsupials, but its role in X-inactivation is unresolved because genome editing in these mammals has only recently become feasible. Using CRISPR-Cas9 in the opossum, we show that RSX is required for the initiation of X-inactivation in marsupial embryos. RSX deletion later, in differentiated cells, causes modest X-gene de-repression, with repressive chromatin marks H3K27me3 and H3K9me3 retained. H2AK119ub is not enriched on the opossum inactive X, revealing divergent Polycomb-mediated regulation in therians. Our findings reveal stage-specific roles of RSX in marsupial X-inactivation and identify conserved and divergent features of X-dosage compensation in mammals.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 08 Jul 2026.

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