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Recent studies, however, have shown that 8\u2010oxoG in gene regulatory elements may serve as an epigenetic mark, and OGG1 has distinct functions in modulating gene expression. Genome\u2010wide mapping of oxidative stress\u2010induced OGG1 enrichment within introns was documented, but its significance has not yet been fully characterized. Here, we explored whether OGG1 recruited to intron 1 of tissue inhibitor of metalloproteinase\u20101 (TIMP1) gene and modulated its expression. Using chromatin and DNA:RNA hybrid immunoprecipitation assays, we report recruitment of OGG1 to the DNA:RNA hybrid in intron 1, where it increases nascent RNA but lowers mRNA levels in O<jats:sub>3<\/jats:sub>\u2010exposed human airway epithelial cells and mouse lungs. Decrease in TIMP1 expression is alleviated by antioxidant administration, small interfering RNA depletion, or inhibition of OGG1 binding to its genomic substrate. <jats:italic>In vitro<\/jats:italic> studies revealed direct interaction between OGG1 and 8\u2010oxoG containing DNA:RNA hybrid, without excision of its substrate. Inhibition of OGG1 binding to DNA:RNA hybrid translated into an increase in TIMP1 expression and a decrease in oxidant\u2010induced lung inflammatory responses as well as airway remodeling. Data documented here reveal a novel molecular link between OGG1 at damaged sites and transcription dynamics that may contribute to oxidative stress\u2010induced cellular and tissue responses.\u2014Pan, L., Wang, H., Luo, J., Zeng J., Pi, J., Liu, H., Liu, C., Ba, X., Qu, X., Xiang Y., Boldogh, I., Qin, X. Epigenetic regulation of TIMP1 expression by 8\u2010oxoguanine DNA glycosylase\u20101 binding to DNA:RNA hybrid. FASEB J. 33, 14159\u201014170 (2019). <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link><\/jats:p>","DOI":"10.1096\/fj.201900993rr","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T18:00:34Z","timestamp":1572026434000},"page":"14159-14170","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Epigenetic regulation of TIMP1 expression by 8\u2010oxoguanine DNA glycosylase\u20101 binding to DNA:RNA hybrid"],"prefix":"10.1096","volume":"33","author":[{"given":"Lang","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Physiology School of Basic Medicine Xiangya Medical School Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Basic Medicine Xiangya Medical School Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Basic Medicine Xiangya Medical School Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Basic Medicine Xiangya Medical School Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Pi","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Basic Medicine Xiangya Medical School Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Basic Medicine Xiangya Medical School Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Basic Medicine Xiangya Medical School Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Ba","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Epigenetics, Ministry of Education Institute of Genetics and Cytology Northeast Normal University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangping","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Basic Medicine Xiangya Medical School Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Basic Medicine Xiangya Medical School Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istvan","family":"Boldogh","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology School of Medicine The University of Texas Medical Branch at Galveston Galveston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqun","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Basic Medicine Xiangya Medical School Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0752rev"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.1070"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S1016-8478(23)13298-5","article-title":"Complexities of DNA base excision repair in mammalian cells","volume":"7","author":"Mitra S.","year":"1997","journal-title":"Mol. 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