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Conserved DNA Methylation Signatures in Early Maternal Separation and in Twins Discordant for CO 2 Sensitivity.
Conserved DNA Methylation Signatures in Early Maternal Separation and in Twins Discordant for CO 2 Sensitivity.
- Source :
-
Scientific reports [Sci Rep] 2018 Feb 02; Vol. 8 (1), pp. 2258. Date of Electronic Publication: 2018 Feb 02. - Publication Year :
- 2018
-
Abstract
- Respiratory and emotional responses to blood-acidifying inhalation of CO <subscript>2</subscript> are markers of some human anxiety disorders, and can be enhanced by repeatedly cross-fostering (RCF) mouse pups from their biological mother to unrelated lactating females. Yet, these dynamics remain poorly understood. We show RCF-associated intergenerational transmission of CO <subscript>2</subscript> 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 <subscript>2</subscript> 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 <subscript>2</subscript> hypersensitivity. In both species, regions bearing differential methylation were associated with neurodevelopment, circulation, and response to pH acidification processes, and notably included the ASIC2 gene. Our data show that CO <subscript>2</subscript> 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.
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 29396481
- Full Text :
- https://doi.org/10.1038/s41598-018-20457-3