{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:09:35Z","timestamp":1790838575220,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T00:00:00Z","timestamp":1551916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["CE17001002"],"award-info":[{"award-number":["CE17001002"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Eesti Teadusagentuur","doi-asserted-by":"publisher","award":["IUT 2\u20102"],"award-info":[{"award-number":["IUT 2\u20102"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002301","name":"Eesti Teadusagentuur","doi-asserted-by":"publisher","award":["PUT1367"],"award-info":[{"award-number":["PUT1367"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011260","name":"FP7 Research infrastructures","doi-asserted-by":"publisher","award":["262055"],"award-info":[{"award-number":["262055"]}],"id":[{"id":"10.13039\/100011260","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["2014\u20102020.4.01.15\u20100012"],"award-info":[{"award-number":["2014\u20102020.4.01.15\u20100012"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>STAT1<\/jats:italic>\n                    gain\u2010of\u2010function (GOF) variants lead to defective Th17 cell development and\u00a0chronic mucocutaneous candidiasis (CMC), but frequently also to autoimmunity. Stimulation of cells with STAT1 inducing cytokines like interferons (IFN) result in hyperphosphorylation and delayed dephosphorylation of GOF STAT1. However, the mechanism how the delayed dephosphorylation exactly causes the increased expression of STAT1\u2010dependent genes, and how the intracellular signal transduction from cytokine receptors is affected, remains unknown. In this study we show that the circulating levels of IFN\u2010\u03b1 were not persistently elevated in\n                    <jats:italic>STAT1<\/jats:italic>\n                    GOF patients. Nevertheless, the expression of interferon signature genes was evident even in the patient with low or undetectable serum IFN\u2010\u03b1 levels. Chromatin immunoprecipitation (ChIP) experiments revealed that the active chromatin mark trimethylation of lysine 4 of histone 3 (H3K4me3), was significantly enriched in areas associated with interferon\u2010stimulated genes in\n                    <jats:italic>STAT1<\/jats:italic>\n                    GOF cells in comparison to cells from healthy donors. This suggests that the chromatin binding of GOF STAT1 variant promotes epigenetic changes compatible with higher gene expression and elevated reactivity to type I interferons, and possibly predisposes for interferon\u2010related autoimmunity. The results also suggest that epigenetic rewiring may be responsible for treatment failure of Janus kinase 1\/2 (JAK1\/2) inhibitors in certain patients.\n                  <\/jats:p>","DOI":"10.1002\/eji.201847955","type":"journal-article","created":{"date-parts":[[2019,2,25]],"date-time":"2019-02-25T23:41:30Z","timestamp":1551138090000},"page":"790-800","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Interferon signature in patients with\n                    <i>STAT1<\/i>\n                    gain\u2010of\u2010function mutation is epigenetically determined"],"prefix":"10.1002","volume":"49","author":[{"given":"Epp","family":"Kaleviste","sequence":"first","affiliation":[{"name":"Department of Biomedicine Institute of Biomedicine and Translational Medicine University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Saare","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Institute of Biomedicine and Translational Medicine University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy Ronan","family":"Leahy","sequence":"additional","affiliation":[{"name":"Department of Paediatric Immunology and Infectious Diseases Our Lady's Children's Hospital  Crumlin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Bondet","sequence":"additional","affiliation":[{"name":"Immunobiology of Dendritic Cells Unit  Inserm U1223, Institut Pasteur Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darragh","family":"Duffy","sequence":"additional","affiliation":[{"name":"Immunobiology of Dendritic Cells Unit  Inserm U1223, Institut Pasteur Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine H.","family":"Mogensen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofie E","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helke","family":"Nurm","sequence":"additional","affiliation":[{"name":"Department of emergency care and acute infections Tallinn Children's Hospital  Tallinn Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie","family":"Ip","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital &amp; UCL Great Ormond Street Institute of Child Health  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E Graham","family":"Davies","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital &amp; UCL Great Ormond Street Institute of Child Health  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Sauer","sequence":"additional","affiliation":[{"name":"Otto Warburg Laboratory, Max Planck Institute for Molecular Genetics  Berlin Germany"},{"name":"Laboratory of Functional Genomics Nutrigenomics and Systems Biology Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine (BIMSB\/BIH)  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann\u2010Christine","family":"Syv\u00e4nen","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Molecular Medicine and Science for Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Milani","sequence":"additional","affiliation":[{"name":"Estonian Genome Center University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4rt","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Institute of Biomedicine and Translational Medicine University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5426-4648","authenticated-orcid":false,"given":"Kai","family":"Kisand","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Institute of Biomedicine and Translational Medicine University of Tartu  Tartu 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