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Yet, these dynamics remain poorly understood. We show RCF-associated intergenerational transmission of CO<jats:sub>2<\/jats:sub>sensitivity in normally-reared mice descending from RCF-exposed females, and describe the accompanying alterations in brain DNA methylation patterns. These epigenetic signatures were compared to DNA methylation profiles of monozygotic twins discordant for emotional reactivity to a CO<jats:sub>2<\/jats:sub>challenge. Altered methylation was consistently associated with repeated elements and transcriptional regulatory regions among RCF-exposed animals, their normally-reared offspring, and humans with CO<jats:sub>2<\/jats:sub>hypersensitivity. In both species, regions bearing differential methylation were associated with neurodevelopment, circulation, and response to pH acidification processes, and notably included the<jats:italic>ASIC2<\/jats:italic>gene. Our data show that CO<jats:sub>2<\/jats:sub>hypersensitivity is associated with specific methylation clusters and genes that subserve chemoreception and anxiety. The methylation status of genes implicated in acid-sensing functions can inform etiological and therapeutic research in this field.<\/jats:p>","DOI":"10.1038\/s41598-018-20457-3","type":"journal-article","created":{"date-parts":[[2018,1,29]],"date-time":"2018-01-29T12:35:20Z","timestamp":1517229320000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Conserved DNA Methylation Signatures in Early Maternal Separation and in Twins Discordant for CO2 Sensitivity"],"prefix":"10.1038","volume":"8","author":[{"given":"Francesca","family":"Giannese","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Luchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Barbiera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Lampis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Zanettini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gun Peggy","family":"Knudsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Scaini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejan","family":"Lazarevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0384-3700","authenticated-orcid":false,"given":"Davide","family":"Cittaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca R.","family":"D\u2019Amato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Battaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,2,2]]},"reference":[{"key":"20457_CR1","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1073\/pnas.98.4.2029","volume":"98","author":"S Brannan","year":"2001","unstructured":"Brannan, S. et al. 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