{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nEP400 is an ATP‐dependent chromatin remodeling factor and an integral component of the Tip60 complex that orchestrates transcriptional programs and cell fate decisions. By interacting with key regulators such as p53 and Myc, EP400 modulates the expression of critical cell cycle genes like p21, thereby influencing processes such as senescence and apoptosis. In normal cells, EP400 helps restrain untimely p21 activation and premature senescence, while in oncogenic contexts, its interactions promote apoptosis through the ARF–p53 pathway."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of the DNA damage response, EP400 is rapidly recruited to double-strand break sites where its ATPase activity drives nucleosome destabilization. This chromatin decompaction is essential for the effective ubiquitination of histones and the subsequent assembly of repair machineries—including RAD51 for homologous recombination—while simultaneously curbing the engagement of error‐prone alternative end joining pathways. In addition, interactions with factors such as ATM may help deliver EP400 to damaged chromatin, and EP400 also contributes to maintaining reactive oxygen species at sub‐damaging levels."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its functions in DNA repair and cell cycle regulation, EP400 plays a pivotal role in chromatin remodeling during transcriptional activation. It facilitates the exchange of canonical histones for variants such as H2A.Z and H3.3—a process vital for the stimulation of gene expression in various contexts including adipogenesis. Imbalances in EP400 levels, as observed in several cancers (colorectal, renal, and breast), correlate with aberrant chromatin states, disrupted senescence, and altered responses to chemotherapy. Although one study sought to develop blood‐based markers for early hepatocellular carcinoma detection, it underscores the clinical relevance of epigenetic regulators like EP400 in disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ho Man Chan, Masako Narita, Scott W Lowe, et al. 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