{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nONECUT1—also known as hepatocyte nuclear factor 6 (HNF6)—is a pivotal transcription factor that orchestrates early developmental programs in the liver and pancreas. It directs the formation and differentiation of pancreatic progenitors and endocrine cells while simultaneously integrating cooperative interactions with other liver‐enriched regulators to fine‐tune genes involved in glucose metabolism and other hepatic functions. Importantly, mutations in ONECUT1 have been associated with syndromic forms of diabetes featuring pancreas hypoplasia and gallbladder anomalies, underscoring its essential role in organogenesis and cellular specification."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its developmental roles, ONECUT1 engages in intricate transcriptional partnerships that modulate chromatin structure and influence cell fate decisions. By physically interacting with coactivators such as CREB‐binding protein and partnering with factors like FOXA2, ONECUT1 not only amplifies transcriptional activation of its targets but also stabilizes these regulatory complexes through post‐translational modifications. Moreover, overexpression studies have demonstrated that ONECUT family members can remodel chromatin accessibility, thereby promoting reprogramming of non–neuronal cells toward a neuronal phenotype."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDeregulation of ONECUT1 has been implicated in a spectrum of diseases. Loss of its expression is linked to pancreatic ductal adenocarcinoma and colorectal liver metastases—suggesting tumor‐suppressive functions in certain contexts—while in other settings, aberrant activation may enhance cellular proliferation, confer resistance to apoptosis (anoikis), and drive metastatic behavior in colorectal and cholangiocarcinomas. In addition, ONECUT1 directly regulates the promoter of coagulation factor IX, a finding that explains aspects of the hemophilia B Leyden phenotype, and it restricts hepatitis B virus gene expression and replication through both transcriptional and post‐transcriptional mechanisms. Collectively, these observations highlight the multifaceted roles of ONECUT1 in development, cellular reprogramming, and disease pathogenesis, marking it as a promising target for therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Francisco M Rausa, Yongjun Tan, Robert H Costa "}, {"type": "b", "children": [{"type": "t", "text": "Association between hepatocyte nuclear factor 6 (HNF-6) and FoxA2 DNA binding domains stimulates FoxA2 transcriptional activity but inhibits HNF-6 DNA binding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.2.437-449.2003"}], "href": "https://doi.org/10.1128/MCB.23.2.437-449.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12509444"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12509444"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Miguel A Maestro, Sylvia F Boj, Reini F Luco, et al. 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