Journal
JOURNAL OF AUTOIMMUNITY
Volume 107, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2019.102357
Keywords
Xist RNA; X-chromosome inactivation; H3K27me3; B cells; Female-biased autoimmunity; NZB/W F1 mice; Sex differences with gene expression
Categories
Funding
- DOD [LR170055: W81XWH-18-1-06]
- NIH [R01-AI134834, T32 AI-055428, F31-GM123604]
Ask authors/readers for more resources
The mechanisms underlying the female-bias in autoimmunity are poorly understood. The contribution of genetic and epigenetic factors from the inactive X chromosome (Xi) are beginning to emerge as critical mediators of autoimmunity in females. Here, we ask how epigenetic features of the Xi change during disease development in B cells from the NZB/W F1 spontaneous mouse model of lupus, which is female-biased. We find that Xist RNA becomes increasingly mislocalized from the Xi with disease onset. While NZB/W F1 naive B cells have H3K27me3 foci on the Xi, which are missing from healthy C57BL/6 and BALB/c mice, these foci are progressively lost in stimulated B cells during disease. Using single-molecule RNA FISH, we show that the X-linked gene Tlr7 is biallelically expressed in similar to 20% of NZB/W F1 B cells, and that the amount of biallelic expression does not change with disease. We also present sex-specific gene expression profiles for diseased NZB/W F1 B cells, and find female-specific upregulation of 20 genes, including the autoimmunity-related genes Cxcl13, Msr1, Igj, and Prdm1. Together, these studies provide important insight into the loss of epigenetic modifications from the Xi and changes with gene expression in a mouse model of female-biased SLE.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available