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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| Language: | English |
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Elsevier
2025-03-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725001226 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Isabel Sierra |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-617fbe2f392248ffaa50832f268a313c |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-617fbe2f392248ffaa50832f268a313c2025-08-20T02:03:46ZengElsevierCell Reports2211-12472025-03-0144311535110.1016/j.celrep.2025.115351B cell stimulation changes the structure and higher-order organization of the inactive X chromosomeIsabel Sierra0Natalie E. Toothacre1Robin H. van der Weide2Claudia D. Lovell3Son C. Nguyen4R. Jordan Barnett5Ashley L. Cook6Han-Seul Ryu7Sarah Pyfrom8Harrison Wang9Daniel Beiting10Jennifer E. Philips-Cremins11Eric F. Joyce12Montserrat C. Anguera13Department of Biomedical Science, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USADepartment of Biomedical Science, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USAHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, Utrecht, the Netherlands; Oncode Institute, University Medical Center Utrecht, Utrecht, the NetherlandsDepartment of Biomedical Science, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USADepartment of Genetics, Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USADepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Biomedical Science, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USADepartment of Biomedical Science, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Genetics, Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USADepartment of Genetics, Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USADepartment of Biomedical Science, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124725001226CP: ImmunologyCP: Molecular biology |
| spellingShingle | 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 B cell stimulation changes the structure and higher-order organization of the inactive X chromosome Cell Reports CP: Immunology CP: Molecular biology |
| title | B cell stimulation changes the structure and higher-order organization of the inactive X chromosome |
| title_full | B cell stimulation changes the structure and higher-order organization of the inactive X chromosome |
| title_fullStr | B cell stimulation changes the structure and higher-order organization of the inactive X chromosome |
| title_full_unstemmed | B cell stimulation changes the structure and higher-order organization of the inactive X chromosome |
| title_short | B cell stimulation changes the structure and higher-order organization of the inactive X chromosome |
| title_sort | b cell stimulation changes the structure and higher order organization of the inactive x chromosome |
| topic | CP: Immunology CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725001226 |
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