{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZNF366, also known as DC‐SCRIPT, is a zinc finger–containing transcriptional coregulator that was first identified as a potent corepressor of the estrogen receptor‐α (ERα). It directly interacts with ERα via zinc finger domains and recruits additional corepressors such as RIP140 and CtBP to suppress estrogen‐responsive gene expression. In addition, genome‐wide association studies have linked polymorphisms near the ZNF366 gene to circulating homocysteine levels, suggesting that its regulatory influence may extend to metabolic pathways beyond classical steroid hormone signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the immune system, ZNF366 (DC‐SCRIPT) is predominantly expressed in dendritic cells (DCs) and serves as an important modulator of nuclear receptor signaling. Within DCs, it regulates glucocorticoid receptor (GR) activity by acting as a corepressor, thereby controlling the expression of key tolerogenic mediators such as glucocorticoid‐inducible leucine zipper (GILZ). Moreover, DC‐SCRIPT influences innate immune responses by modulating NF‐κB activation and TLR‐induced cytokine production, notably affecting IL-10 levels. These functions underscore its role in fine-tuning the balance between inflammation and tolerance during immune responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in hormone and immune signaling, ZNF366 has emerged as a significant factor in cancer biology. In breast cancer, its corepressive action on ERα signaling is associated with cell cycle arrest through regulation of tumor suppressor genes such as CDKN2B, and its expression levels serve as an independent prognostic marker in ERα‐positive tumors. Similarly, studies in prostate cancer have implicated DC‐SCRIPT in modulating nuclear receptor pathways relevant to tumor progression. Reviews of nuclear receptor crosstalk further highlight ZNF366/DC‐SCRIPT as a bifunctional coregulator integrating metabolic and inflammatory signals, thereby influencing disease outcomes across diverse tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jorge Lopez-Garcia, Manikandan Periyasamy, Ross S Thomas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF366 is an estrogen receptor corepressor that acts through CtBP and histone deacetylases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkl875"}], "href": "https://doi.org/10.1093/nar/gkl875"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17085477"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17085477"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Anders Mälarstig, Alfonso Buil, Juan Carolos Souto, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "DC-SCRIPT regulates glucocorticoid receptor function and expression of its target GILZ in dendritic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1201776"}], "href": "https://doi.org/10.4049/jimmunol.1201776"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23440419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23440419"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jonas Nørskov Søndergaard, Susanna Poghosyan, Saartje Hontelez, et al. 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