{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:57:24Z","timestamp":1783339044980,"version":"3.54.6"},"reference-count":91,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["2015"],"award-info":[{"award-number":["2015"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p><jats:italic>Borrelia burgdorferi<\/jats:italic>, a tick-vectored spirochete bacteria best known for causing Lyme disease, has been found to induce physiological and behavioural changes in its tick vector that can increase tick fitness and its ability to transmit the bacteria. The mechanism by which this bacterium modulates these changes remains unknown. Epigenetics plays a central role in transducing external and internal microbiome environmental influences to the organism, so we investigated DNA methylation and the expression of a key histone modification enzyme in <jats:italic>Borrelia<\/jats:italic>-infected and uninfected <jats:italic>Ixodes scapularis<\/jats:italic> ticks. DNA methylation of the pericentromeric tandem repeats family, <jats:italic>Ixodes scapularis<\/jats:italic> Repeats (ISR), were assessed by methylated-DNA immunoprecipitation (MeDIP) followed by qPCR of the ISR regions. DNA methylation of the ISR sequences was found. The different repeats had different levels of DNA methylation, however, these levels were not significantly affected by the presence or absence of <jats:italic>B. burgdorferi<\/jats:italic>. The epigenetic regulator <jats:italic>euchromatic histone lysine methyltransferase 2<\/jats:italic> (<jats:italic>EHMT2<\/jats:italic>) is recognized as having a key role in modulating the organismal stress response to infections. To assess <jats:italic>EHMT2<\/jats:italic> transcription in <jats:italic>Borrelia<\/jats:italic>-infected and uninfected ticks, real-time reverse transcriptase PCR was performed. Uninfected ticks had over 800X lower <jats:italic>EHMT2<\/jats:italic> expression than infected ticks. This study is among the first to identify a gene that may be involved in producing epigenetic differences in ticks depending on infection status and lays the groundwork for future epigenetic studies of <jats:italic>I. scapularis<\/jats:italic> in response to <jats:italic>B. burgdorferi<\/jats:italic> as well as other pathogens that these ticks transmit.<\/jats:p>","DOI":"10.1371\/journal.pone.0324546","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T17:42:39Z","timestamp":1749145359000},"page":"e0324546","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Epigenetic responses in Borrelia-infected Ixodes scapularis ticks: Over-expression of euchromatic histone lysine methyltransferase 2 and no change in DNA methylation"],"prefix":"10.1371","volume":"20","author":[{"given":"Grace Hadley","family":"MacIntosh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra C.","family":"Nuyens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Vickery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Berthold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1191-2585","authenticated-orcid":true,"given":"Vett K.","family":"Lloyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"issue":"1","key":"pone.0324546.ref001","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s12915-021-01025-0","article-title":"The epigenetic regulator G9a attenuates stress-induced resistance and metabolic transcriptional programs across different stressors and species","volume":"19","author":"H Riahi","year":"2021","journal-title":"BMC Biol"},{"issue":"1","key":"pone.0324546.ref002","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.tree.2020.09.003","article-title":"Towards an evolutionary theory of stress responses","volume":"36","author":"B Taborsky","year":"2021","journal-title":"Trends Ecol Evol"},{"issue":"15","key":"pone.0324546.ref003","doi-asserted-by":"crossref","first-page":"3040","DOI":"10.1111\/mec.14769","article-title":"Evolution of heat-shock protein expression underlying adaptive responses to environmental stress","volume":"27","author":"B Chen","year":"2018","journal-title":"Mol Ecol"},{"issue":"6","key":"pone.0324546.ref004","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/s41576-021-00438-5","article-title":"Molecular mechanisms of transgenerational epigenetic inheritance","volume":"23","author":"MH Fitz-James","year":"2022","journal-title":"Nat Rev Genet"},{"issue":"5","key":"pone.0324546.ref005","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1007\/s10620-017-4538-6","article-title":"Influences of the gut microbiota on DNA methylation and histone modification","volume":"62","author":"J Ye","year":"2017","journal-title":"Dig Dis Sci"},{"key":"pone.0324546.ref006","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.cois.2019.02.008","article-title":"Where the baculoviruses lead, the caterpillars follow: baculovirus-induced alterations in caterpillar behaviour","volume":"33","author":"SN Gasque","year":"2019","journal-title":"Curr Opin Insect Sci"},{"issue":"1","key":"pone.0324546.ref007","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1186\/s12864-015-1812-x","article-title":"Gene expression during zombie ant biting behavior reflects the complexity underlying fungal parasitic behavioral manipulation","volume":"16","author":"C de Bekker","year":"2015","journal-title":"BMC Genomics"},{"issue":"3","key":"pone.0324546.ref008","doi-asserted-by":"crossref","DOI":"10.1111\/pim.12909","article-title":"Hijacking time: how Ophiocordyceps fungi could be using ant host clocks to manipulate behavior","volume":"44","author":"C de Bekker","year":"2022","journal-title":"Parasite Immunol"},{"key":"pone.0324546.ref009","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/j.1365-3024.2011.01344.x","article-title":"Filarial and Wolbachia genomics","volume":"34","author":"AL Scott","year":"2012","journal-title":"Parasite Immunol"},{"issue":"6","key":"pone.0324546.ref010","article-title":"Infection with a virulent strain of wolbachia disrupts genome wide-patterns of cytosine methylation in the mosquito aedes aegypti. 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