B cell stimulation changes the structure and higher-order organization of the inactive X chromosome

B cell stimulation changes the structure and higher-order organization of the inactive X chromosome

Summary: X chromosome inactivation (XCI) equalizes X-linked gene expression between sexes. B cells exhibit dynamic XCI, with Xist RNA/heterochromatic marks absent on the inactive X (Xi) in naive B cells but returning following mitogenic stimulation. The impact of dynamic XCI on Xi structure and main...

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Main Authors: Isabel Sierra, Natalie E. Toothacre, Robin H. van der Weide, Claudia D. Lovell, Son C. Nguyen, R. Jordan Barnett, Ashley L. Cook, Han-Seul Ryu, Sarah Pyfrom, Harrison Wang, Daniel Beiting, Jennifer E. Philips-Cremins, Eric F. Joyce, Montserrat C. Anguera
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Cell Reports
Subjects:
CP: Immunology
CP: Molecular biology
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725001226
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Summary:Summary: X chromosome inactivation (XCI) equalizes X-linked gene expression between sexes. B cells exhibit dynamic XCI, with Xist RNA/heterochromatic marks absent on the inactive X (Xi) in naive B cells but returning following mitogenic stimulation. The impact of dynamic XCI on Xi structure and maintenance was previously unknown. Here, we find dosage compensation of the Xi with state-specific XCI escape genes in naive and in vitro-activated B cells. Allele-specific OligoPaints indicate similar Xi and active X (Xa) territories in B cells that are less compact than in fibroblasts. Allele-specific Hi-C reveals a lack of TAD-like structures on the Xi of naive B cells and stimulation-induced alterations in TAD-like boundary strength independent of gene expression. Notably, Xist deletion in B cells changes TAD boundaries and large-scale Xi compaction. Altogether, our results uncover B cell-specific Xi plasticity, which could underlie sex-biased biological mechanisms.
ISSN:2211-1247

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