ArticleProceedings of the National Academy of Sciences of the United States of America2021
The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 112 citations in OpenAlex.
- Epigenetic regulation of humoral immunity: molecular mechanisms, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- A distinct effector B cell population drives autoantibody production in SARS-CoV-2 infection.Immunity · 2026Article
- Sex-dependent mechanisms in rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- Epigenetic regulation of B cell tolerance and dysfunction in autoimmune disease.Nature reviews. Immunology · 2026Review
- SPEN Loss Drives Extrafollicular Diffuse Large B-cell Lymphoma with Female-Specific Lethality and Therapeutic Vulnerabilities.Cancer discovery · 2026Article
- Interferon-Mediated Regulation of Memory B Cell Identity and Function.Immunological reviews · 2026Review
- Escape from X-chromosome inactivation: from gene discovery to regulatory mechanisms.Biochemical Society transactions · 2026Review
- Machine learning reveals X chromosome transcriptional signatures that classify systemic lupus erythematosus in females.BMC rheumatology · 2026Article
- Female mice with a Xist deletion in B cells can develop lupus-associated phenotypes.Cell reports · 2026Article
- Sex differences in response to longevity interventions.Ageing research reviews · 2026Review
- Genome-Wide DNA Methylation Changes Induced by High-Fat Diet and Methyl Donor Supplementation in Female Lupus Models: An Exploratory Study.Molecular nutrition & food research · 2026Article
- Xist RNA dependent and independent mechanisms regulate dynamic X chromosome inactivation in B lymphocytes.Cell reports · 2026Article
- The X Factor in Immunity: Sex Differences Shaped by the X Chromosome.Immunological reviews · 2026Review
- Sex differences in immune modulation: implications for infection, inflammation, and nutritional supplementation.Biology of sex differences · 2026Review
- The impact of X chromosome inactivation on human health.Frontiers in genetics · 2026Review
- Long noncoding RNA regulation of immunity.Nature immunology · 2026Review
- Genomic Instability and Clonal Hematopoiesis in the Deep-Space Environment: The Role of Sex-Chromosome Asymmetry and High-LET Radiation.Current stem cell reports · 2026Article
- TLR7 and TLR9 have overlapping but distinct roles in systemic lupus erythematosus and Sjögren's disease.Frontiers in immunology · 2026Review
- Impact of somatic XIST deletions on ongoing XIST expression and inactive X silencing and heterochromatin.Human molecular genetics · 2025Article
- The sex-biased chromatin modifier SMC1A promotes autoimmunity by shaping inflammatory pathways in patients with SLE.Nature communications · 2025Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Systemic lupus erythematous (SLE) is a female-predominant disease characterized by autoimmune B cells and pathogenic autoantibody production. Individuals with two or more X chromosomes are at increased risk for SLE, suggesting that X-linked genes contribute to the observed sex bias of this disease. To normalize X-linked gene expression between sexes, one X in female cells is randomly selected for transcriptional silencing through X-chromosome inactivation (XCI), resulting in allele-specific enrichment of epigenetic modifications, including histone methylation and the long noncoding RNA XIST/Xist on the inactive X (Xi). As we have previously shown that epigenetic regulation of the Xi in female lymphocytes from mice is unexpectedly dynamic, we used RNA fluorescence in situ hybridization and immunofluorescence to profile epigenetic features of the Xi at the single-cell level in human B cell subsets from pediatric and adult SLE patients and healthy controls. Our data reveal that abnormal XCI maintenance in B cells is a feature of SLE. Using single-cell and bulk-cell RNA sequencing datasets, we found that X-linked immunity genes escape XCI in specific healthy human B cell subsets and that human SLE B cells exhibit aberrant expression of X-linked genes and XIST RNA interactome genes. Our data reveal that mislocalized XIST RNA, coupled with a dramatic reduction in heterochromatic modifications at the Xi in SLE, predispose for aberrant X-linked gene expression from the Xi, thus defining a genetic and epigenetic pathway that affects X-linked gene expression in human SLE B cells and likely contributes to the female bias in SLE.
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