{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n IFNG‐AS1 – also referred to as NeST or TMEVPG1 – is a long noncoding RNA located adjacent to the interferon‐γ (IFNG) gene that plays a critical role in the epigenetic regulation and transcriptional activation of IFNG in T helper 1 (Th1) cells. Studies have demonstrated that IFNG‐AS1 acts by recruiting chromatin‐modifying complexes (for example, by binding components such as WDR5) to induce histone modifications at the IFNG locus, thereby enhancing IFNG expression and promoting a Th1‐specific gene transcription program."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Moreover, the positive regulatory role of IFNG‐AS1 has been implicated in various immune and inflammatory contexts. For instance, upregulated IFNG‐AS1 expression correlates with enhanced IFNG production in autoimmune conditions such as Hashimoto’s thyroiditis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", as well as in infectious diseases including brucellosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and during host defense responses where both the DNA element and the RNA transcript contribute to proper chromatin organization and immune protection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In contrast, reduced IFNG‐AS1 expression has been observed in certain pathological settings—such as psychiatric disorders and coronary artery disease—where its decreased levels are associated with diminished IFNG transcript levels"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", suggesting that tightly controlled IFNG‐AS1 expression is essential for normal immune function."}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to directly modulating IFNG transcription, IFNG‐AS1 has been shown to influence cellular processes beyond classic immune regulation. Its dysregulation is linked to altered Th1 responses in diverse disease states including multiple sclerosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", certain cancers such as breast and colon adenocarcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", and even in conditions affecting epithelial cell survival in colitis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Furthermore, complex regulatory feedback loops have been suggested whereby IFNG‐AS1 not only promotes IFNG transcription but may also be subject to negative feedback in settings where IFNG is overexpressed, as observed in immune thrombocytopenia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that IFNG‐AS1 functions as a key enhancer RNA involved in the precise regulation of IFNG expression, with its altered expression contributing to the pathogenesis of various immune‐mediated, infectious, neoplastic, and inflammatory disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "17"}]}, {"type": "t", "text": " These studies collectively underscore the importance of IFNG‐AS1 as both a modulator of IFNG transcription and a potential biomarker or therapeutic target in diseases where aberrant IFNG-driven immunity is a central feature.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J Antonio Gomez, Orly L Wapinski, Yul W Yang, et al. 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