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Nutrient metabolism, substrate processing, and detoxification are circadian controlled in livers. However, how the clock genes respond to toxins and influence toxicity keeps unclear. We identified the clock gene <jats:italic>Per1<\/jats:italic> was specifically elevated in mice exposed to toxins such as carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>). Mice lacking <jats:italic>Per1<\/jats:italic> slowed down the metabolic rate of toxins including CCl<jats:sub>4<\/jats:sub>, capsaicin, and acetaminophen, exhibiting relatively more residues in the plasma. Liver injury and fibrosis induced by acute and chronic CCl<jats:sub>4<\/jats:sub> exposure were markedly alleviated in <jats:italic>Per1<\/jats:italic>-deficient mice. These processes involved the binding of PER1 protein and hepatocyte nuclear factor-1alpha (HNF-1\u03b1), which enhances the recruitment of HNF-1\u03b1 to cytochrome P450 2E1 (<jats:italic>Cyp2e1<\/jats:italic>) promoter and increases <jats:italic>Cyp2e1<\/jats:italic> expression, thereby promoting metabolism for toxins in the livers. These results indicate that PER1 mediates the metabolism of toxins and appropriate suppression of <jats:italic>Per1<\/jats:italic> response is a potential therapeutic target for toxin-induced hepatotoxicity.<\/jats:p>","DOI":"10.1038\/s41419-020-03343-7","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T20:14:49Z","timestamp":1610482489000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Period1 mediates rhythmic metabolism of toxins by interacting with CYP2E1"],"prefix":"10.1038","volume":"12","author":[{"given":"Wenhao","family":"Ge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-9103","authenticated-orcid":false,"given":"Jianfa","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"3343_CR1","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1038\/nature00965","volume":"418","author":"SM Reppert","year":"2002","unstructured":"Reppert, S. 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