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Here, we identify Activating Transcription Factor 7 (ATF7) as a key regulator of mitophagy in colonic epithelial cells. Integrative transcriptomic and epigenomic analyses of patient\u2010derived mucosal samples revealed marked ATF7 downregulation and widespread activation of inflammatory pathways. Chromatin immunoprecipitation and luciferase reporter assays demonstrated that ATF7 directly binds to and activates the promoter of PINK1, a master regulator of mitophagy. Genetic ablation of ATF7 or PINK1 in human epithelial cells impaired mitophagy, disrupted mitochondrial membrane potential, and increased reactive oxygen species. In\u00a0vivo, intestinal epithelial cell\u2010specific knockout of ATF7 or PINK1 exacerbated dextran sulfate sodium\u2010induced colitis, with greater epithelial injury, elevated cytokine production, and transcriptional activation of TNF, NF\u2010kappaB, and inflammatory bowel disease signalling pathways. These results establish ATF7 as a critical transcriptional regulator linking mitochondrial homeostasis to epithelial resilience in the inflamed colon.<\/jats:p>","DOI":"10.1111\/jcmm.70831","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T04:17:47Z","timestamp":1756959467000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Epigenomic Profiling Positions\n                    <scp>ATF7<\/scp>\n                    as a Core Regulator of Colonic Inflammation"],"prefix":"10.1111","volume":"29","author":[{"given":"Fang","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Department of Gastroenterology The First Affiliated Hospital of Shihezi University  Shihezi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidong","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Department of Endoscopy and Digestive System Guizhou Provincial People's Hospital  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junrong","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan 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