{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:30:14Z","timestamp":1790775014548,"version":"4.1.0"},"reference-count":203,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T00:00:00Z","timestamp":1561593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2013\/11\/B\/NZ1\/00091"],"award-info":[{"award-number":["2013\/11\/B\/NZ1\/00091"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2014\/15\/B\/NZ2\/01079"],"award-info":[{"award-number":["2014\/15\/B\/NZ2\/01079"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2015\/17\/D\/NZ5\/03444"],"award-info":[{"award-number":["2015\/17\/D\/NZ5\/03444"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2016\/23\/B\/NZ5\/00573"],"award-info":[{"award-number":["2016\/23\/B\/NZ5\/00573"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2018\/29\/B\/NZ4\/00771"],"award-info":[{"award-number":["2018\/29\/B\/NZ4\/00771"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["17GRNT32910002"],"award-info":[{"award-number":["17GRNT32910002"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hyperhomocysteinemia (HHcy) exerts a wide range of biological effects and is associated with a number of diseases, including cardiovascular disease, dementia, neural tube defects, and cancer. Although mechanisms of HHcy toxicity are not fully uncovered, there has been a significant progress in their understanding. The picture emerging from the studies of homocysteine (Hcy) metabolism and pathophysiology is a complex one, as Hcy and its metabolites affect biomolecules and processes in a tissue- and sex-specific manner. Because of their connection to one carbon metabolism and editing mechanisms in protein biosynthesis, Hcy and its metabolites impair epigenetic control of gene expression mediated by DNA methylation, histone modifications, and non-coding RNA, which underlies the pathology of human disease. In this review we summarize the recent evidence showing that epigenetic dysregulation of gene expression, mediated by changes in DNA methylation and histone N-homocysteinylation, is a pathogenic consequence of HHcy in many human diseases. These findings provide new insights into the mechanisms of human disease induced by Hcy and its metabolites, and suggest therapeutic targets for the prevention and\/or treatment.<\/jats:p>","DOI":"10.3390\/ijms20133140","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T08:19:13Z","timestamp":1561623553000},"page":"3140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["Dysregulation of Epigenetic Mechanisms of Gene Expression in the Pathologies of Hyperhomocysteinemia"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0791-5057","authenticated-orcid":false,"given":"Joanna","family":"Per\u0142a-Kaj\u00e1n","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biotechnology, Pozna\u0144 University of Life Sciences, 60-637 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5845-4409","authenticated-orcid":false,"given":"Hieronim","family":"Jakubowski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, Pozna\u0144 University of Life Sciences, 60-637 Pozna\u0144, Poland"},{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School, International Center for Public Health, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s00726-006-0432-9","article-title":"Mechanisms of homocysteine toxicity in humans","volume":"32","author":"Twardowski","year":"2007","journal-title":"Amino Acids"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1146\/annurev.med.60.041807.123308","article-title":"The treatment of hyperhomocysteinemia","volume":"60","author":"Maron","year":"2009","journal-title":"Annu. 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