{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPOU2F1 (also known as Oct‐1) is a ubiquitous transcription factor that plays a central role in the regulation of gene expression by partnering with various cofactors. Early studies revealed that it is essential for S‐phase–dependent histone H2B transcription through its incorporation into the OCA‐S coactivator complex that links transcription to cellular metabolic (redox) state"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", and that Oct‐1 is a component of nuclear bodies (OPT domains) enriched at genomic fragile sites, suggesting a role in the maintenance of genome integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of stress and inflammation, POU2F1 modulates the expression of key response genes. It directly influences cytokine gene expression by binding to promoter elements of the tumor necrosis factor gene, thereby interacting with NF‐κB components to fine‐tune inflammatory signals"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and it cooperates with BRCA1 to activate the GADD45 promoter during DNA damage."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, Oct‐1 occupies overlapping binding sites in the C-reactive protein promoter to modulate its transcription in response to pro‐inflammatory signals"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while its allele–specific binding to regulatory polymorphisms also contributes to lactase persistence by enhancing the lactase promoter activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Additionally, HDAC inhibitor–driven induction of GADD45 requires intact Oct‐1 and NF‐Y binding sites."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPOU2F1 is also pivotal during development and in endocrine regulation. It cooperates with Sox2 to synergistically regulate neural developmental programs"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and performs complex DNA target searches via its bipartite DNA-binding domains."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In reproductive tissues, Oct‐1 helps govern neuron-specific expression of gonadotropin-releasing hormone by directly interacting with TALE homeodomain proteins"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "and by acting as a repressor at the GnRH receptor promoter"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", with further modulation by Groucho-related gene corepressors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " In addition, Oct‐1 is implicated in the regulation of developmental signaling pathways, such as those governing FZD5 expression in pluripotent and cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer, dysregulated POU2F1 activity contributes to tumorigenesis and progression across a variety of tissues. Through cooperation with STAT5, Oct‐1 enhances cyclin D1 transcription and thereby supports cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Aberrantly high expression of POU2F1 has been correlated with aggressive phenotypes in prostate"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ", esophageal"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ", cervical"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ", colon"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": ", head and neck"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", and osteosarcoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " In liver cancer, microRNA-mediated suppression of POU2F1 reduces CAPN6 expression, thereby impairing cell proliferation and promoting apoptosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": ", and in glioblastoma, AMPK-dependent phosphorylation events alter Oct‐1 activity to regulate miR-451 levels and promote cellular adaptation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn non-cancerous tissues, POU2F1 modulates vascular and metabolic functions. In endothelial cells, Oct‐1 governs the transcriptional response to shear stress by binding to ARE-like elements within the Nox4 promoter"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": ", and it represses the cytokine-induced expression of adhesion molecules, thereby contributing to vascular quiescence."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": " Oct‐1 additionally regulates immune gene expression by controlling HLA-C promoter activity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": ", and in muscle cells it mediates androgen receptor–dependent repression of the muscle atrophy gene MAFbx."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": " Furthermore, Oct‐1 directly activates catalase expression, thus participating in antioxidant defense"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": ", while its role in redox-regulated histone transcription also highlights its integration of metabolic signals into gene control."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPost‐translational modifications fine–tune the transcriptional activity of POU2F1 under stress conditions. DNA-dependent protein kinase–mediated phosphorylation of Oct‐1 modulates its stability and transactivation potential in response to DNA damage"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": ", and oxidative/genotoxic stress induces selective phosphorylation events that alter its DNA-binding selectivity, facilitating an appropriate stress response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, genetic and epigenetic modulation of POU2F1 impacts human health span. 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