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AKI is primarily caused by renal hypoxia, and it causes epigenetic alterations, known as hypoxic memory. 3\u2010Deazaneplanocin A (Dznep), an inhibitor of histone modification, suppresses renal fibrosis and the expression of tissue inhibitor of metalloproteinases\u20102 (TIMP2), a profibrotic factor, in mouse ischemia\u2013reperfusion models. The current study investigated the epigenetic regulation of TIMP2 in human kidney 2 (HK\u20102) cells. The expression of TIMP2 was upregulated in HK\u20102 cells under hypoxic conditions and was suppressed by Dznep. ChIP\u2010qPCR showed that Dznep reduced the amount of H3K4me3 at the promoter region of the TIMP2 gene under hypoxic condition. Formaldehyde\u2010assisted isolation of regulatory elements\u2010qPCR of the TIMP2 gene showed that Dznep reduced open chromatin area. In addition, based on ChIP\u2010qPCR of hypoxia\u2010inducible factor 1 alpha (HIF1\u03b1), Dznep inhibited the binding of HIF1\u03b1 to the TIMP2 gene under hypoxic conditions. The reporter assays for the binding region of HIF1\u03b1 showed enhanced transcriptional activity by hypoxia. Dznep suppresses the expression of TIMP2 under hypoxic conditions by inhibiting the binding of HIF1\u03b1 to the TIMP2 gene.<\/jats:p>","DOI":"10.14814\/phy2.15810","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T03:07:06Z","timestamp":1694747226000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dznep, a histone modification inhibitor, inhibits HIF1\u03b1 binding to TIMP2 gene and suppresses TIMP2 expression under hypoxia"],"prefix":"10.14814","volume":"11","author":[{"given":"Tomotaka","family":"Yamazaki","sequence":"first","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3454-5127","authenticated-orcid":false,"given":"Imari","family":"Mimura","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Kurata","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuhiro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Rheumatology and Endocrinology Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaomi","family":"Nangaku","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1813599"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.379"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u2010291x(86)90048\u20103"},{"issue":"2","key":"e_1_2_9_5_1","first-page":"111","article-title":"Tissue inhibitors of metalloproteinases: Structure, regulation and biological functions","volume":"74","author":"Gomez D. 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