{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:44:42Z","timestamp":1790995482111,"version":"4.1.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"34","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,8,26]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Graves disease (GD) is an autoimmune disease caused by interactions between genetic, epigenetic, and environmental factors. The thyrotropin receptor (\n                    <jats:italic>TSHR<\/jats:italic>\n                    ) is the major autoantigen in GD and is a key GD susceptibility gene. SNPs in intron 1 of the\n                    <jats:italic>TSHR<\/jats:italic>\n                    are associated with GD, but the causative variant and the mechanisms are unknown. By mapping epigenetic modifications induced by IFN\u03b1, a viral-induced cytokine triggering GD, we pinpointed the causative variant in intron 1 of the\n                    <jats:italic>TSHR<\/jats:italic>\n                    . We demonstrate that the disease-associated variant interacts epigenetically with a transcriptional repressor, promyelocytic leukemia zinc finger protein, and reduces thymic\n                    <jats:italic>TSHR<\/jats:italic>\n                    expression, leading to escape from tolerance and autoimmunity to the TSHR. These genetic\u2013epigenetic interactions leading to decreased thymic self-antigen expression reveal a universal mechanism in autoimmunity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1408821111","type":"journal-article","created":{"date-parts":[[2014,8,14]],"date-time":"2014-08-14T00:10:36Z","timestamp":1407975036000},"page":"12562-12567","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":84,"title":["Genetic\u2013epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity"],"prefix":"10.1073","volume":"111","author":[{"given":"Mihaela","family":"Stefan","sequence":"first","affiliation":[{"name":"Division of Endocrinology and"},{"name":"James J. Peters Veterans Administration Medical Center, Bronx, NY 10468"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengguo","family":"Wei","sequence":"additional","affiliation":[{"name":"Departments of cMedicine Bioinformatics Core and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheuk Wun","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erlinda S.","family":"Concepcion","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"William B.","family":"Inabnet","sequence":"additional","affiliation":[{"name":"Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Owen","sequence":"additional","affiliation":[{"name":"Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of cMedicine Bioinformatics Core and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaron","family":"Tomer","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and"},{"name":"James J. 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