B cell stimulation changes the structure and higher-order organization of the inactive X chromosome
Authors:
- Robin H. van der WeideRWRobin H. van der Weide
Preprint
Abstract
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 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.Keywords
All Related Versions
- Published version: Cell Reports, 44 (3), 115351.
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