{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DNA methyltransferase 1 (DNMT1) is the primary maintenance enzyme responsible for faithfully copying established DNA methylation patterns during DNA replication and cell division. This activity ensures the stable propagation of epigenetic states that underlie gene silencing and cellular identity. DNMT1 is recruited to hemimethylated CpG sites through its interaction with accessory factors such as UHRF1, which preferentially binds these intermediates and tethers DNMT1 at replication foci."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer cells, experimental depletion of DNMT1 results in a dramatic reduction in global and gene-specific methylation, leading to the reactivation of tumor-suppressor genes. Such observations underscore its critical role in maintaining aberrant methylation patterns that facilitate neoplastic proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, DNMT1 exhibits high processivity—rapidly and accurately modifying nascent DNA strands to mirror the parental methylation pattern—which is essential for proper epigenetic inheritance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n DNMT1 function is further modulated by its association with chromatin-modifying enzymes. For instance, its direct binding to the histone methyltransferase G9a couples DNA methylation with histone H3 lysine 9 methylation to reinforce transcriptional repression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, DNMT1 activity can be attenuated through interactions with specific RNAs. Transcripts emanating from loci such as CEBPA bind DNMT1 and prevent local methylation, thereby promoting gene-specific demethylation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n A noncanonical isoform of DNMT1 localizes to mitochondria, where it mediates cytosine methylation of mitochondrial DNA and influences mitochondrial gene expression and metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, aberrant regulation of DNMT1 by microRNAs has been implicated in disease states; for example, miR-29b indirectly down-regulates DNMT1 in acute myeloid leukemia, while miR-21 and miR-148a target DNMT1 in CD4+ T cells in systemic lupus erythematosus, linking DNMT1 dysfunction to pathological hypomethylation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the central nervous system, DNMT1—often in concert with de novo methyltransferases like DNMT3a—is essential for maintaining genomic methylation patterns that underlie synaptic plasticity, learning, and memory."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight the multifaceted role of DNMT1 in safeguarding epigenetic memory, coordinating with chromatin regulators, and modulating gene expression in diverse biological settings. Disruption of DNMT1 activity not only perturbs normal development and neuronal function but also contributes to oncogenesis and autoimmune disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Magnolia Bostick, Jong Kyong Kim, Pierre-Olivier Estève, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UHRF1 plays a role in maintaining DNA methylation in mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1147939"}], "href": "https://doi.org/10.1126/science.1147939"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17673620"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17673620"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ina Rhee, Kurtis E Bachman, Ben Ho Park, et al. 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