title: Methylation ofavpr1ain the cortex of wild prairie voles: effects of CpG position and polymorphism.
abstract: DNA methylation can cause stable changes in neuronal gene expression, but we know little about its role in individual differences in the wild. In this study, we focus on the vasopressin 1a receptor (avpr1a), a gene extensively implicated in vertebrate social behaviour, and explore natural variation in DNA methylation, genetic polymorphism and neuronal gene expression among 30 wild prairie voles (Microtus ochrogaster). Examination of CpG density across 8 kb of the locus revealed two distinct CpG islands overlapping promoter and first exon, characterized by few CpG polymorphisms. We used a targeted bisulfite sequencing approach to measure DNA methylation across approximately 3 kb ofavpr1ain the retrosplenial cortex, a brain region implicated in male space use and sexual fidelity. We find dramatic variation in methylation across theavrp1alocus, with pronounced diversity near the exon-intron boundary and in a genetically variable putative enhancer within the intron. Among our wild voles, differences in corticalavpr1aexpression correlate with DNA methylation in this putative enhancer, but not with the methylation status of the promoter. We also find an unusually high number of polymorphic CpG sites (polyCpGs) in this focal enhancer. One polyCpG within this enhancer (polyCpG 2170) may drive variation in expression either by disrupting transcription factor binding motifs or by changing local DNA methylation and chromatin silencing. Our results contradict some assumptions made within behavioural epigenetics, but are remarkably concordant with genome-wide studies of gene regulation.
authors.affiliation: Department of Integrative Biology , University of Texas at Austin , Austin, TX , USA.
authors.forename: M
authors.identifier: 0000-0002-3145-9397
authors.initials: M
authors.lastname: Okhovat
authors.affiliation: Department of Integrative Biology , University of Texas at Austin , Austin, TX , USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Maguire
authors.affiliation: Department of Integrative Biology , University of Texas at Austin , Austin, TX , USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Phelps
keywords: CpG polymorphism; DNA methylation; Microtus ochrogaster; avpr1a; epigenetics; retrosplenial cortex