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One marker of nitrative stress is the formation of 3\u2010nitrotyrosine, or protein tyrosine nitration (PTN), which has been observed during inflammation and tissue injury; however, the role of PTN in the progression or possibly the pathogenesis of disease is still unclear. We show in a model of alcohol\u2010induced liver injury that an increase in PTN occurs in hepatocyte nuclei within the liver of wild\u2010type male C57BL\/6J mice following chronic ethanol exposure (28\u2009days). High\u2010resolution mass spectrometric analysis of isolated hepatic nuclei revealed several novel sites of tyrosine nitration on histone proteins. Histone nitration sites were validated by tandem mass spectrometry (MS\/MS) analysis of representative synthetic nitropeptides equivalent in sequence to the respective nitrotyrosine sites identified in vivo. We further investigated the potential structural impact of the novel histone H3 Tyr41 (H3Y41) nitration site identified using molecular dynamics (MD) simulations. MD simulations of the nitrated and non\u2010nitrated forms of histone H3Y41 showed significant structural changes at the DNA interface upon H3Y41 nitration. The results from this study suggest that, in addition to other known post\u2010translational modifications that occur on histone proteins (e.g., acetylation and methylation), PTN could induce chromatin structural changes, possibly affecting gene transcription processes associated with the development of alcohol\u2010induced liver injury.<\/jats:p>","DOI":"10.1002\/jms.4713","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T01:25:55Z","timestamp":1614389155000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Site\u2010specific identification and validation of hepatic histone nitration in vivo: Implications for alcohol\u2010induced liver injury"],"prefix":"10.1002","volume":"56","author":[{"given":"Crystina L.","family":"Kriss","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Microbiology and Molecular Biology University of South Florida  4202 E. Fowler Ave Tampa FL 33620 USA"},{"name":"Department of Cardiovascular Regeneration Houston Methodist Research Institute  6607 Bertner Ave Houston TX 77030 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nalvi","family":"Duro","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Microbiology and Molecular Biology University of South Florida  4202 E. Fowler Ave Tampa FL 33620 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Owen W.","family":"Nadeau","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Albany College of Pharmacy and Health Sciences  261 Mountain View Dr Colchester VT 05446 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Guergues","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Albany College of Pharmacy and Health Sciences  261 Mountain View Dr Colchester VT 05446 USA"},{"name":"MSRC Proteomics Core Laboratory Vanderbilt University, Medical Research Building III  Nashville TN 37232 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Chavez\u2010Chiang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Microbiology and Molecular Biology University of South Florida  4202 E. Fowler Ave Tampa FL 33620 USA"},{"name":"Department of Tumor Biology H. Lee Moffitt Cancer Center &amp; Research Institute  12902 Magnolia Drive, SRB\u20103 Tampa FL 33612 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley E.","family":"Culver\u2010Cochran","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Microbiology and Molecular Biology University of South Florida  4202 E. Fowler Ave Tampa FL 33620 USA"},{"name":"Division of Experimental Hematology and Cancer Biology Cincinnati Children's Hospital Medical Center  Cincinnati OH 45229 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dale","family":"Chaput","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Microbiology and Molecular Biology University of South Florida  4202 E. 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