{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:54:25Z","timestamp":1790013265879,"version":"4.0.1"},"reference-count":122,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>X chromosome inactivation (XCI) is a crucial genetic regulatory mechanism in female cells, wherein one of the two X chromosomes is randomly silenced to balance gene expression between sexes. Despite the overall silencing, approximately 15%\u201330% of human genes escape XCI, leading to their biallelic expression in females. Many studies have highlighted the phenomenon of XCI skewing, where the inactivation is preferentially biased towards one X chromosome. XCI escape and XCI skewing are significantly associated with various health issues, including autoimmune disorders, neurodevelopmental disorders (NDDS), cardiovascular diseases (CVD) and cancer, etc. This review aims to provide a comprehensive overview of the mechanisms underlying XCI, its roles across different genders and disease states, and to explore the intricate relationship between XCI and human health. By emphasizing the significance of understanding XCI, this article seeks to shed light on potential therapeutic targets and avenues for further research in the field.<\/jats:p>","DOI":"10.3389\/fgene.2026.1845863","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T22:10:38Z","timestamp":1780006238000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The impact of X chromosome inactivation on human health"],"prefix":"10.3389","volume":"17","author":[{"given":"Junyi","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, The First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]},{"name":"School of Medicine, Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, The First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1161\/CIRCULATIONAHA.121.054108","article-title":"Genes that escape X chromosome inactivation modulate sex differences in valve myofibroblasts","volume":"145","author":"Aguado","year":"2022","journal-title":"Circulation"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.exphem.2020.01.008","article-title":"60 years of clonal hematopoiesis research: from X-chromosome inactivation studies to the identification of driver mutations","volume":"83","author":"Ayachi","year":"2020","journal-title":"Exp. Hematol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"113810","DOI":"10.1016\/j.intimp.2024.113810","article-title":"Expression and prognostic impact of hypoxia- and immune escape-related genes in triple-negative breast cancer: a comprehensive analysis","volume":"146","author":"Ba","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13072-021-00404-9","article-title":"Contribution of genetic and epigenetic changes to escape from X-chromosome inactivation","volume":"14","author":"Balaton","year":"2021","journal-title":"Epigenet. Chromatin."},{"key":"B5","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13072-021-00386-8","article-title":"Cross-species examination of X-chromosome inactivation highlights domains of escape from silencing","volume":"14","author":"Balaton","year":"2021","journal-title":"Epigenet. Chromatin."},{"key":"B6","doi-asserted-by":"publisher","first-page":"328","DOI":"10.3389\/fcell.2019.00328","article-title":"Forged by DXZ4, FIRRE, and ICCE: how tandem repeats shape the active and inactive x chromosome","volume":"7","author":"Bansal","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e1002001","DOI":"10.1371\/journal.pgen.1002001","article-title":"RNF12 activates Xist and is essential for X chromosome inactivation","volume":"7","author":"Barakat","year":"2011","journal-title":"PLoS Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/gb-2010-11-6-213","article-title":"Escape from X inactivation in mice and humans","volume":"11","author":"Berletch","year":"2010","journal-title":"Genome Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1093\/hmg\/ddaf160","article-title":"Impact of somatic XIST deletions on ongoing XIST expression and inactive X silencing and heterochromatin","volume":"34","author":"Bhangu","year":"2025","journal-title":"Hum. Mol. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"637","DOI":"10.3390\/cells12040637","article-title":"Sexually dimorphic alterations in the transcriptome and behavior with loss of histone demethylase KDM5C","volume":"12","author":"Bonefas","year":"2023","journal-title":"Cells"},{"key":"B11","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/0092-8674(92)90520-m","article-title":"The human XIST gene: analysis of a 17 Kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus","volume":"71","author":"Brown","year":"1992","journal-title":"Cell"},{"key":"B12","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13293-023-00527-6","article-title":"X chromosome inactivation skewing is common in advanced carotid atherosclerotic lesions in females and predicts secondary peripheral artery events","volume":"14","author":"Buono","year":"2023","journal-title":"Biol. Sex. Differ."},{"key":"B13","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/s42003-025-07691-y","article-title":"Defective X-chromosome inactivation and cancer risk in women","volume":"8","author":"C\u00e1ceres","year":"2025","journal-title":"Commun. Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"20160358","DOI":"10.1098\/rstb.2016.0358","article-title":"Human X chromosome inactivation and reactivation: implications for cell reprogramming and disease","volume":"372","author":"Cantone","year":"2017","journal-title":"Philos. Trans. R. Soc. Lond. B. Biol. Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.3390\/cells12182245","article-title":"Establishing the link between X-Chromosome aberrations and TP53 status, with breast cancer patient outcomes","volume":"12","author":"Caramia","year":"2023","journal-title":"Cells"},{"key":"B16","doi-asserted-by":"publisher","first-page":"E668","DOI":"10.1073\/pnas.1715124115","article-title":"A mixed modality approach towards Xi reactivation for Rett syndrome and other X-linked disorders","volume":"115","author":"Carrette","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"B17","doi-asserted-by":"publisher","first-page":"R106","DOI":"10.1186\/ar2759","article-title":"Analysis of skewed X-chromosome inactivation in females with rheumatoid arthritis and autoimmune thyroid diseases","volume":"11","author":"Chabchoub","year":"2009","journal-title":"Arthritis Res. Ther."},{"key":"B18","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/s43856-025-01220-y","article-title":"Whole-genome profiling of age- and sex-associated DNA methylation signatures in human plasma cell-free DNA","volume":"5","author":"Chen","year":"2025","journal-title":"Commun. Med. (Lond)."},{"key":"B19","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s13148-024-01666-2","article-title":"Polycomb repressive complex 2 and its core component EZH2: potential targeted therapeutic strategies for head and neck squamous cell carcinoma","volume":"16","author":"Cheng","year":"2024","journal-title":"Clin. Epigenet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1007\/s00109-022-02227-x","article-title":"Epigenetic mechanisms regulate sex-specific bias in disease manifestations","volume":"100","author":"Chlamydas","year":"2022","journal-title":"J. Mol. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1093\/hmg\/ddq516","article-title":"Ftx is a non-coding RNA which affects xist expression and chromatin structure within the X-inactivation center region","volume":"20","author":"Chureau","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"B22","doi-asserted-by":"publisher","first-page":"31","DOI":"10.12688\/wellcomeopenres.15711.1","article-title":"The role of the xist 5\u2019 m6A region and RBM15 in X chromosome inactivation","volume":"5","author":"Coker","year":"2020","journal-title":"Wellcome Open Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/31275","article-title":"Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals","volume":"393","author":"Costanzi","year":"1998","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.1242\/dev.127.11.2283","article-title":"Histone macroH2A1 is concentrated in the inactive X chromosome of female preimplantation mouse embryos","volume":"127","author":"Costanzi","year":"2000","journal-title":"Development"},{"key":"B25","doi-asserted-by":"publisher","first-page":"9074","DOI":"10.3390\/ijms22169074","article-title":"Molecular mechanisms of skewed X-chromosome inactivation in female hemophilia patients-lessons from wide genome analyses","volume":"22","author":"Dardik","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1080\/15622975.2025.2517040","article-title":"Escape genes from X-chromosome inactivation: new insights into candidate genes for intellectual disability in females","volume":"26","author":"de Oliveira","year":"2025","journal-title":"World J. Biol. Psychiatry."},{"key":"B27","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1080\/07357907.2021.1981364","article-title":"X-linked tumor suppressor genes act as presumed contributors in the sex chromosome-autosome crosstalk in cancers","volume":"40","author":"Dhabhai","year":"2022","journal-title":"Cancer Invest."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.3390\/genes13071268","article-title":"A novel hypothesis on choroideremia-manifesting female carriers: could CHM in-frame variants exert a dominant negative effect? A case report","volume":"13","author":"Di Giosaffatte","year":"2022","journal-title":"Genes"},{"key":"B29","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1007\/s12041-015-0574-1","article-title":"X-chromosome inactivation and escape","volume":"94","author":"Disteche","year":"2015","journal-title":"J. Genet."},{"key":"B30","doi-asserted-by":"publisher","first-page":"a040196","DOI":"10.1101\/cshperspect.a040196","article-title":"The molecular and nuclear dynamics of X-chromosome inactivation","volume":"14","author":"Dossin","year":"2022","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/s41586-020-1974-9","article-title":"SPEN integrates transcriptional and epigenetic control of X-inactivation","volume":"578","author":"Dossin","year":"2020","journal-title":"Nature"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2082","DOI":"10.3390\/cancers12082082","article-title":"Study of the female sex survival advantage in melanoma-a focus on X-linked epigenetic regulators and immune responses in two cohorts","volume":"12","author":"Emran","year":"2020","journal-title":"Cancers"},{"key":"B33","doi-asserted-by":"publisher","first-page":"334","DOI":"10.3390\/antiox12020334","article-title":"Relationship between glucose-6-phosphate dehydrogenase deficiency, X-chromosome inactivation and inflammatory markers","volume":"12","author":"Errigo","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"B34","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1186\/s12864-024-10240-2","article-title":"Identification of skewed X chromosome inactivation using exome and transcriptome sequencing in patients with suspected rare genetic disease","volume":"25","author":"Fadra","year":"2024","journal-title":"BMC Genomics"},{"key":"B35","doi-asserted-by":"publisher","first-page":"219","DOI":"10.3389\/fcell.2019.00219","article-title":"X inactivation and escape: epigenetic and structural features","volume":"7","author":"Fang","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s12915-025-02137-7","article-title":"CTCF-Mediated insulation and chromatin environment modulate car5b escape from X inactivation","volume":"23","author":"Fang","year":"2025","journal-title":"BMC Biol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1186\/s13023-022-02423-5","article-title":"Turner syndrome: french national diagnosis and care rotocol (NDCP; national diagnosis and care protocol)","volume":"17","author":"Fiot","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e666","DOI":"10.1212\/NXG.0000000000000666","article-title":"Not just loss-of-function variations: identification of a hypermorphic variant in a patient with a CDKL5 missense substitution","volume":"8","author":"Frasca","year":"2022","journal-title":"Neurol. Genet."},{"key":"B39","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.devcel.2012.06.011","article-title":"Smchd1-dependent and -independent pathways determine developmental dynamics of CpG island methylation on the inactive X chromosome","volume":"23","author":"Gendrel","year":"2012","journal-title":"Dev. Cell"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1038\/s41431-023-01324-w","article-title":"Skewed X-chromosome inactivation in unsolved neurodevelopmental disease cases can guide re-evaluation for X-linked genes","volume":"31","author":"Giovenino","year":"2023","journal-title":"Eur. J. Hum. Genet."},{"key":"B41","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1016\/j.stemcr.2021.03.007","article-title":"Attrition of X chromosome inactivation in aged hematopoietic stem cells","volume":"16","author":"Grigoryan","year":"2021","journal-title":"Stem Cell Rep."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.3389\/fimmu.2019.02160","article-title":"Characterization of Cxorf21 provides molecular insight into female-bias immune response in SLE pathogenesis","volume":"10","author":"Harris","year":"2019","journal-title":"Front. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"856917","DOI":"10.3389\/fmed.2022.856917","article-title":"A genetic association test accounting for skewed X-inactivation with application to biotherapy immunogenicity in patients with autoimmune diseases","volume":"9","author":"H\u00e4ssler","year":"2022","journal-title":"Front. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/s0092-8674(01)00598-0","article-title":"Methylation of histone H3 at lys-9 is an early mark on the X chromosome during X inactivation","volume":"107","author":"Heard","year":"2001","journal-title":"Cell"},{"key":"B45","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1038\/s43587-025-00856-8","article-title":"Aging promotes reactivation of the barr body at distal chromosome regions","volume":"5","author":"Hoelzl","year":"2025","journal-title":"Nat. Aging."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e2100","DOI":"10.1002\/mgg3.2100","article-title":"Nance-horan syndrome pedigree due to a novel microdeletion and skewed X chromosome inactivation","volume":"11","author":"Huang","year":"2023","journal-title":"Mol. Genet. Genomic Med."},{"key":"B47","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/s41594-022-00739-1","article-title":"Xist spatially amplifies SHARP\/SPEN recruitment to balance chromosome-wide silencing and specificity to the X chromosome","volume":"29","author":"Jachowicz","year":"2022","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/j.ebiom.2015.06.012","article-title":"Over-expression of XIST, the master gene for X chromosome inactivation, in females with major affective disorders","volume":"2","author":"Ji","year":"2015","journal-title":"EBioMedicine"},{"key":"B49","doi-asserted-by":"publisher","first-page":"103084","DOI":"10.1016\/j.jaut.2023.103084","article-title":"Impaired dynamic X-chromosome inactivation maintenance in T cells is a feature of spontaneous murine SLE that is exacerbated in female-biased models","volume":"139","author":"Jiwrajka","year":"2023","journal-title":"J. Autoimmun."},{"key":"B50","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1136\/annrheumdis-2012-201851","article-title":"Fine mapping of Xq28: both MECP2 and IRAK1 contribute to risk for systemic lupus erythematosus in multiple ancestral groups","volume":"72","author":"Kaufman","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/s13148-021-01121-6","article-title":"Methylation status of genes escaping from X-chromosome inactivation in patients with X-chromosome rearrangements","volume":"13","author":"Kawashima","year":"2021","journal-title":"Clin. Epigenet."},{"key":"B52","doi-asserted-by":"publisher","first-page":"7101","DOI":"10.3390\/ijms26157101","article-title":"Understanding sex differences in autoimmune diseases: immunologic mechanisms","volume":"26","author":"Kim","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"139","DOI":"10.17116\/jnevro2025125011139","article-title":"A case of becker muscular dystrophy in a woman with skewed X-chromosome inactivation","volume":"125","author":"Korotkova","year":"2025","journal-title":"Zh. Nevrol. Psikhiatr. Im. S. S. Korsakova"},{"key":"B54","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1002\/gepi.22091","article-title":"An integrative approach to assess X-chromosome inactivation using allele-specific expression with applications to epithelial ovarian cancer","volume":"41","author":"Larson","year":"2017","journal-title":"Genet. Epidemiol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/s41431-022-01233-4","article-title":"Expanding the genetics and phenotypic spectrum of Lysine-specific demethylase 5C (KDM5C): a report of 13 novel variants","volume":"31","author":"Leonardi","year":"2023","journal-title":"Eur. J. Hum. Genet."},{"key":"B56","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13073-020-00736-3","article-title":"Exploratory analysis of age and sex dependent DNA methylation patterns on the X-chromosome in whole blood samples","volume":"12","author":"Li","year":"2020","journal-title":"Genome Med."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1016\/j.gendis.2022.04.007","article-title":"Long noncoding RNA XIST: mechanisms for X chromosome inactivation, roles in sex-biased diseases, and therapeutic opportunities","volume":"9","author":"Li","year":"2022","journal-title":"Genes Dis."},{"key":"B58","doi-asserted-by":"publisher","first-page":"533","DOI":"10.3760\/cma.j.cn511374-20230808-00048","article-title":"Clinical features and genetic analysis of 17 Chinese pedigrees affected with X-linked intellectual disability","volume":"41","author":"Li","year":"2024","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"B59","doi-asserted-by":"publisher","first-page":"114","DOI":"10.3779\/j.issn.1009-3419.2025.105.01","article-title":"FCN3 can serve as a potential biomarker for prognosis and immunotherapy of lung squamous cell carcinoma","volume":"28","author":"Li","year":"2025","journal-title":"Chin. J. Lung Cancer"},{"key":"B60","doi-asserted-by":"publisher","first-page":"e36051","DOI":"10.1097\/MD.0000000000036051","article-title":"Oxeiptosis core genes and their multi-omics analysis in hepatocellular carcinoma","volume":"102","author":"Lin","year":"2023","journal-title":"Med. Baltim."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13293-024-00683-3","article-title":"KDM6A facilitates xist upregulation at the onset of X inactivation","volume":"16","author":"Lin","year":"2025","journal-title":"Biol. Sex. Differ."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.7150\/ijbs.57178","article-title":"CRL4-DCAF8L1 regulates BRCA1 and BARD1 protein stability","volume":"18","author":"Liu","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"102543","DOI":"10.1016\/j.coi.2025.102543","article-title":"More x\u2019s, more problems: how contributions from the X chromosomes enhance female predisposition for autoimmunity","volume":"93","author":"Lovell","year":"2025","journal-title":"Curr. Opin. Immunol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"102902","DOI":"10.1016\/j.conb.2024.102902","article-title":"Emerging X-linked genes associated with neurodevelopmental disorders in females","volume":"88","author":"Lukin","year":"2024","journal-title":"Curr. Opin. Neurobiol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"439","DOI":"10.3760\/cma.j.cn511374-20200513-00344","article-title":"Analysis and prenatal diagnosis of FMR1 gene mutations among patients with unexplained mental retardation","volume":"38","author":"Luo","year":"2021","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"B66","doi-asserted-by":"publisher","first-page":"1273596","DOI":"10.3389\/fcvm.2023.1273596","article-title":"Role of vascular smooth muscle cell clonality in atherosclerosis","volume":"10","author":"Luo","year":"2023","journal-title":"Front. Cardiovasc Med."},{"key":"B67","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1038\/190372a0","article-title":"Gene action in the X-chromosome of the mouse (mus musculus L.)","volume":"190","author":"Lyon","year":"1961","journal-title":"Nature"},{"key":"B68","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature14443","article-title":"The xist lncRNA interacts directly with SHARP to silence transcription through HDAC3","volume":"521","author":"McHugh","year":"2015","journal-title":"Nature"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1086\/301858","article-title":"Familial skewed X inactivation and X-linked mutations: unbalanced X inactivation is a powerful means to ascertain X-linked genes that affect cell proliferation","volume":"62","author":"Migeon","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"B122","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1172\/JCI34470","article-title":"A skewed view of X chromosome inactivation","volume":"118","author":"Minks","year":"2008","journal-title":"J. Clin. Invest."},{"key":"B70","doi-asserted-by":"publisher","first-page":"120709","DOI":"10.1016\/j.lfs.2022.120709","article-title":"The potential of B7-H6 as a therapeutic target in cancer immunotherapy","volume":"304","author":"Mohammadi","year":"2022","journal-title":"Life Sci."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1182\/bloodadvances.2021005664","article-title":"Azacitidine is a potential therapeutic drug for pyridoxine-refractory female X-linked sideroblastic anemia","volume":"6","author":"Morimoto","year":"2022","journal-title":"Blood Adv."},{"key":"B72","doi-asserted-by":"publisher","first-page":"6034","DOI":"10.3390\/ijms26136034","article-title":"Sex differences in hypertension risk: insights from placental genomics and pregnancy-driven vascular programming","volume":"26","author":"Moustakli","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B73","doi-asserted-by":"publisher","first-page":"104465","DOI":"10.1016\/j.isci.2022.104465","article-title":"Single-cell analysis reveals X upregulation is not global in pre-gastrulation embryos","volume":"25","author":"Naik","year":"2022","journal-title":"iScience"},{"key":"B74","doi-asserted-by":"publisher","first-page":"789","DOI":"10.4049\/jimmunol.1800931","article-title":"Cutting edge: CXCR3 escapes X chromosome inactivation in T cells during infection: potential implications for sex differences in immune responses","volume":"203","author":"Oghumu","year":"2019","journal-title":"J. Immunol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"lqad052","DOI":"10.1093\/nargab\/lqad052","article-title":"Refining the genomic determinants underlying escape from X-chromosome inactivation","volume":"5","author":"Peeters","year":"2023","journal-title":"Nar. Genomics Bioinf"},{"key":"B76","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1126\/science.1084274","article-title":"Role of histone H3 lysine 27 methylation in X inactivation","volume":"300","author":"Plath","year":"2003","journal-title":"Science"},{"key":"B77","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1083\/jcb.200409026","article-title":"Developmentally regulated alterations in polycomb repressive complex 1 proteins on the inactive X chromosome","volume":"167","author":"Plath","year":"2004","journal-title":"J. Cell Biol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"7991","DOI":"10.1073\/pnas.1803792115","article-title":"Pharmacological reactivation of inactive X-linked Mecp2 in cerebral cortical neurons of living mice","volume":"115","author":"Przanowski","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"B79","doi-asserted-by":"publisher","first-page":"e2024624118","DOI":"10.1073\/pnas.2024624118","article-title":"The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients","volume":"118","author":"Pyfrom","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B80","doi-asserted-by":"publisher","first-page":"eadd4666","DOI":"10.1126\/scitranslmed.add4666","article-title":"Multiplex epigenome editing of MECP2 to rescue Rett syndrome neurons","volume":"15","author":"Qian","year":"2023","journal-title":"Sci. Transl. Med."},{"key":"B81","doi-asserted-by":"publisher","first-page":"102472","DOI":"10.1016\/j.stemcr.2025.102472","article-title":"Gene reactivation upon erosion of X chromosome inactivation in female hiPSCs is predictable yet variable and persists through differentiation","volume":"20","author":"Raposo","year":"2025","journal-title":"Stem Cell Rep."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1038\/s41556-023-01266-x","article-title":"GATA transcription factors drive initial xist upregulation after fertilization through direct activation of long-range enhancers","volume":"25","author":"Ravid Lustig","year":"2023","journal-title":"Nat. Cell Biol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"146644","DOI":"10.1016\/j.brainres.2019.146644","article-title":"Sex differences in Mecp2-mutant Rett syndrome model mice and the impact of cellular mosaicism in phenotype development","volume":"1729","author":"Ribeiro","year":"2020","journal-title":"Brain Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"e78263","DOI":"10.7554\/eLife.78263","article-title":"Age acquired skewed X chromosome inactivation is associated with adverse health outcomes in humans","volume":"11","author":"Roberts","year":"2022","journal-title":"Elife"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1136\/ard-2024-225585","article-title":"Haematopoietic stem cell-derived immune cells have reduced X chromosome inactivation skewing in systemic lupus erythematosus","volume":"83","author":"Roberts","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"B86","doi-asserted-by":"publisher","first-page":"eabe7500","DOI":"10.1126\/science.abe7500","article-title":"Time-resolved structured illumination microscopy reveals key principles of xist RNA spreading","volume":"372","author":"Rodermund","year":"2021","journal-title":"Science"},{"key":"B87","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s42000-020-00241-7","article-title":"Oncologic manifestations of Klinefelter syndrome","volume":"19","author":"Rojas","year":"2020","journal-title":"Hormones"},{"key":"B88","doi-asserted-by":"publisher","first-page":"5475","DOI":"10.1128\/MCB.24.12.5475-5484.2004","article-title":"Differential histone H3 lys-9 and lys-27 methylation profiles on the X chromosome","volume":"24","author":"Rougeulle","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"e180071","DOI":"10.1172\/JCI180071","article-title":"Epigenetic developmental mechanisms underlying sex differences in cancer","volume":"134","author":"Rubin","year":"2024","journal-title":"J. Clin. Invest."},{"key":"B90","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1016\/j.cels.2022.10.002","article-title":"Somatic XIST activation and features of X chromosome inactivation in Male human cancers","volume":"13","author":"Sadagopan","year":"2022","journal-title":"Cell Syst."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.3389\/fonc.2019.01459","article-title":"XIST and TSIX: novel cancer immune biomarkers in PD-L1-overexpressing breast cancer patients","volume":"9","author":"Salama","year":"2020","journal-title":"Front. Oncol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1111\/cen.13857","article-title":"Skewed X chromosome inactivation in girls and female adolescents with autoimmune thyroid disease","volume":"89","author":"Santiwatana","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s40246-018-0173-3","article-title":"Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes","volume":"12","author":"Sathishkumar","year":"2018","journal-title":"Hum. Genomics"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1101\/gr.275677.121","article-title":"Inferring genes that escape X-chromosome inactivation reveals important contribution of variable escape genes to sex-biased diseases","volume":"31","author":"Sauteraud","year":"2021","journal-title":"Genome Res."},{"key":"B95","doi-asserted-by":"publisher","first-page":"3110","DOI":"10.1038\/sj.emboj.7601187","article-title":"Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing","volume":"25","author":"Schoeftner","year":"2006","journal-title":"EMBO J."},{"key":"B96","doi-asserted-by":"publisher","first-page":"1479814","DOI":"10.3389\/fimmu.2025.1479814","article-title":"The toll like receptor 7 pathway and the sex bias of systemic lupus erythematosus","volume":"16","author":"Scofield","year":"2025","journal-title":"Front. Immunol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/s13258-021-01199-5","article-title":"Epigenome editing: targeted manipulation of epigenetic modifications in plants","volume":"44","author":"Shin","year":"2022","journal-title":"Genes Genomics"},{"key":"B98","doi-asserted-by":"publisher","first-page":"e11216","DOI":"10.7759\/cureus.11216","article-title":"Skewed inactivation of X chromosome: a cause of hemophilia manifestation in carrier females","volume":"12","author":"Shoukat","year":"2020","journal-title":"Cureus"},{"key":"B99","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.stemcr.2022.12.005","article-title":"Unusual X chromosome inactivation maintenance in female alveolar type 2 cells is correlated with increased numbers of X-linked escape genes and sex-biased gene expression","volume":"18","author":"Sierra","year":"2023","journal-title":"Stem Cell Rep."},{"key":"B100","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/j.cell.2007.02.025","article-title":"Further evidence for BRCA1 communication with the inactive X chromosome","volume":"128","author":"Silver","year":"2007","journal-title":"Cell"},{"key":"B101","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s13293-025-00750-3","article-title":"X-linked transcriptome dysregulation across immune cells in systemic lupus erythematosus","volume":"16","author":"Soares","year":"2025","journal-title":"Biol. Sex. Differ."},{"key":"B102","doi-asserted-by":"publisher","first-page":"eaap8855","DOI":"10.1126\/sciimmunol.aap8855","article-title":"TLR7 escapes X chromosome inactivation in immune cells","volume":"3","author":"Souyris","year":"2018","journal-title":"Sci. Immunol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1093\/eurjpc\/zwaf224","article-title":"Sex chromosomes and cardiovascular disease","volume":"33","author":"Spiering","year":"2026","journal-title":"Eur. J. Prev. Cardiol."},{"key":"B104","doi-asserted-by":"publisher","first-page":"999442","DOI":"10.3389\/fgene.2022.999442","article-title":"Case report: de novo DDX3X mutation caused intellectual disability in a female with skewed X-chromosome inactivation on the mutant allele","volume":"13","author":"Sun","year":"2022","journal-title":"Front. Genet."},{"key":"B105","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1167\/tvst.12.12.7","article-title":"Visual acuity-related outer retinal structural parameters on swept source optical coherence tomography and angiography in XLRS patients and carriers","volume":"12","author":"Tao","year":"2023","journal-title":"Transl. Vis. Sci. Technol."},{"key":"B106","doi-asserted-by":"publisher","first-page":"e51989","DOI":"10.15252\/embr.202051989","article-title":"H4K20me1 and H3K27me3 are concurrently loaded onto the inactive X chromosome but dispensable for inducing gene silencing","volume":"22","author":"Tjalsma","year":"2021","journal-title":"EMBO Rep."},{"key":"B107","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s13059-024-03286-8","article-title":"X-chromosome inactivation in human iPSCs provides insight into X-regulated gene expression in autosomes","volume":"25","author":"Topa","year":"2024","journal-title":"Genome Biol."},{"key":"B108","doi-asserted-by":"publisher","first-page":"e2029","DOI":"10.1002\/mgg3.2029","article-title":"X-chromosomal inactivation patterns in women with fabry disease","volume":"10","author":"Wagenh\u00e4user","year":"2022","journal-title":"Mol. Genet. Genomic Med."},{"key":"B109","doi-asserted-by":"publisher","first-page":"2949","DOI":"10.1007\/s00018-020-03469-z","article-title":"Abnormal X chromosome inactivation and tumor development","volume":"77","author":"Wang","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"B110","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s12195-023-00762-2","article-title":"Angiotensin II increases oxidative stress and inflammation in female, but not Male, endothelial cells","volume":"16","author":"Weber","year":"2023","journal-title":"Cell. Mol. Bioeng."},{"key":"B111","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1016\/j.devcel.2022.07.007","article-title":"Variability of cross-tissue X-chromosome inactivation characterizes timing of human embryonic lineage specification events","volume":"57","author":"Werner","year":"2022","journal-title":"Dev. Cell"},{"key":"B112","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1007\/s00059-018-4691-5","article-title":"Blood pressure and collateral circulation in acute ischemic stroke","volume":"44","author":"Wufuer","year":"2019","journal-title":"Herz"},{"key":"B113","doi-asserted-by":"publisher","first-page":"285","DOI":"10.3390\/biology9090285","article-title":"A glance of p53 functions in brain development, neural stem cells, and brain cancer","volume":"9","author":"Xiong","year":"2020","journal-title":"Biol. (Basel)"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1101\/2025.09.14.676175v1","article-title":"Single- cell genomic copy number evolution reveals frequent loss of the Y chromosome in esophageal adenocarcinoma","author":"Yin","year":"2025","journal-title":"bioRxiv [preprint]"},{"key":"B115","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s13293-023-00544-5","article-title":"TLR8 escapes X chromosome inactivation in human monocytes and CD4+ T cells","volume":"14","author":"Youness","year":"2023","journal-title":"Biol. Sex. Differ."},{"key":"B116","doi-asserted-by":"publisher","first-page":"2523","DOI":"10.1093\/hmg\/ddaa131","article-title":"Skewed allelic expression on X chromosome associated with aberrant expression of XIST on systemic lupus erythematosus lymphocytes","volume":"29","author":"Zhang","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"B117","doi-asserted-by":"publisher","first-page":"5571","DOI":"10.1038\/s41467-024-49764-2","article-title":"X chromosome dosage drives statin-induced dysglycemia and mitochondrial dysfunction","volume":"15","author":"Zhang","year":"2024","journal-title":"Nat. Commun."},{"key":"B118","doi-asserted-by":"publisher","first-page":"1642956","DOI":"10.3389\/fimmu.2025.1642956","article-title":"Sex chromosomes\/hormones and the tumor microenvironment of non-reproductive cancers","volume":"16","author":"Zhang","year":"2025","journal-title":"Front. Immunol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"e1010556","DOI":"10.1371\/journal.pgen.1010556","article-title":"Escape from X-inactivation in twins exhibits intra- and inter-individual variability across tissues and is heritable","volume":"19","author":"Zito","year":"2023","journal-title":"PLoS Genet."},{"key":"B120","doi-asserted-by":"publisher","first-page":"2519035","DOI":"10.1080\/13685538.2025.2519035","article-title":"Recommendations for diagnosis and treatment of the aging Male with Klinefelter syndrome","volume":"28","author":"Zitzmann","year":"2025","journal-title":"Aging Male"},{"key":"B121","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.cell.2018.11.041","article-title":"The implication of early chromatin changes in X chromosome inactivation","volume":"176","author":"\u017bylicz","year":"2019","journal-title":"Cell"}],"updated-by":[{"DOI":"10.3389\/fgene.2026.1898696","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000}}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1845863\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T07:01:03Z","timestamp":1782716463000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1845863\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":122,"alternative-id":["10.3389\/fgene.2026.1845863"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2026.1845863","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"article-number":"1845863"}}