Remodeling and compaction of the inactive X is regulated by Xist during female B cell activation

Anguera, M.; Sierra, I.; Nguyen, S. C.; Barnett, R. J.; Cook, A.; Ryu, H.-S.; Beethem, Z.; Phillips-Cremins, J. E.; Joyce, E. F.

doi:10.1101/2022.10.19.512821

bioRxiv · 10.1101/2022.10.19.512821

Remodeling and compaction of the inactive X is regulated by Xist during female B cell activation

Anguera, M.·Sierra, I.·Nguyen, S. C.·Barnett, R. J.·Cook, A.·Ryu, H.-S.·Beethem, Z.·Phillips-Cremins, J. E.·Joyce, E. F.

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Abstract

X Chromosome Inactivation (XCI) equalizes X-linked gene expression between sexes. B cells exhibit unusually dynamic XCI, as Xist RNA/heterochromatic marks on the inactive X (Xi) are absent in naive B cells, but return following mitogenic stimulation. Xi gene expression analysis supports dosage compensation, but reveals high levels of XCI escape genes in both naive and activated B cells. Allele-specific OligoPaints indicate similar Xi and Xa territories in B cells that is less compact than in fibroblasts. Allele-specific Hi-C maps reveal a lack of TAD-like structures on the Xi of naive B cells, and alterations in TADs and stronger TAD boundaries at Xi escape genes after mitogenic stimulation. Notably, Xist deletion in B cells reduces Xi compaction and changes TAD boundaries, independent of its localization to the Xi. Our findings provide the first evidence that Xi compaction/small scale organization in lymphocytes impact XCI maintenance and female biased X-linked gene expression.

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Anguera, M., Sierra, I., Nguyen, S. C., Barnett, R. J., Cook, A., Ryu, H.-S., Beethem, Z., Phillips-Cremins, J. E., Joyce, E. F.. 2022-10-21. Remodeling and compaction of the inactive X is regulated by Xist during female B cell activation. https://doi.org/10.1101/2022.10.19.512821

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