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

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.

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Publication Details

Journal
Cell Reports
Published
2025-02-26
DOI
https://doi.org/10.1016/j.celrep.2025.115351
Citations
4
Primary Topic
Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Type
article
Field-Weighted Citation Impact
7.27
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article

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

Son C. Nguyen, Eric F. Joyce, Sarah Pyfrom, Harrison Wang et al.
4 citations
Cell Reports
Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
7.27
article

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

Son C. Nguyen, Eric F. Joyce, Sarah Pyfrom, Harrison Wang, Montserrat C. Anguera, Claudia D. Lovell, Robin H. van der Weide, Han-Seul Ryu, Jennifer E. Phillips‐Cremins, Ashley L. Cook, Daniel P. Beiting, Natalie E. Toothacre, Isabel Sierra, R. Jordan Barnett
article en
4 citations

Abstract

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.

Cell ReportsVol. 44(3)
Royal Netherlands Academy of Arts and Sciences (NL), Translational Therapeutics (United States) (US), University of Pennsylvania (US)
Zero hunger
Openalex Percentile: Top 4%
Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
7.27
DOIOpen Access PDFOpenAlex
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