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First, analysis of differentially expressed genes in CIRI based on the GEO dataset GSE119121 revealed that BACH1 was upregulated in CIRI. BACH1 level was prominently increased in middle cerebral artery occlusion (MCAO)\/reperfusion model and oxygen\u2013glucose deprivation\/reoxygenation cell model. Further, knock\u2010down of BACH1 markedly reduced iron ion concentration, ROS production, 4\u2010HNE and lipid peroxidation levels and facilitated GSH content, cell viability and protein levels of GPX4 and SLC7A11, while an pcDNA\u2010KDM4C or pcDNA\u2010COX2 combined with BACH1 siRNA could not enhance this effect. Mechanistically, BACH1 bound on the KDM4C promoter to transcriptionally activate its expression. Besides, KDM4C could occupy the promoter locus of the COX2 gene, promoting the COX2 expression by eliminating H3K9me3. Overexpression of KDM4C or COX2 overturned the effects of BACH1 inhibition. In vivo findings displayed that brain infraction, pathological damage and neuronal loss rate in MCAO mice were conspicuously decreased after BACH1 knock\u2010down. This study reveals that BACH1 encourages ferroptosis in neuroblastoma cells and CIRI mouse brain tissues by activating KDM4C\u2010mediated COX2 demethylation.<\/jats:p>","DOI":"10.1111\/ejn.16035","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T00:54:02Z","timestamp":1683766442000},"page":"2194-2214","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["BACH1 encourages ferroptosis by activating KDM4C\u2010mediated COX2 demethylation after cerebral ischemia\u2013reperfusion injury"],"prefix":"10.1111","volume":"58","author":[{"given":"Tianqi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology The Fourth Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meimei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology The Fourth Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology The Fourth Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9298-8826","authenticated-orcid":false,"given":"Xinya","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurology The Fourth Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"},{"name":"Department of Neurology The Second Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuobo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology The Fourth Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000855"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.09.014"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.015779"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2020.147216"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.624529"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.23126"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103378"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.12.009"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116795"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118660"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.102617"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1615\/IntJMedMushrooms.v17.i10.90"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joim.2020.01.008"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201902584R"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/1587922"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21249729"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612827666210105124529"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051651"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000496922"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.009548"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.11.2835"},{"key":"e_1_2_10_23_1","first-page":"587","article-title":"Identification of dynamic co\u2010expression networks in peripheral blood of rats after middle cerebral artery occlusion","volume":"48","author":"Pan Z.","year":"2019","journal-title":"Zhejiang da Xue Xue Bao. 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