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Methylation of avpr1a in the cortex of wild prairie voles: effects of CpG position and polymorphism

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...

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Autores principales: Okhovat, M., Maguire, S. M., Phelps, S. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society Publishing 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319330/
https://www.ncbi.nlm.nih.gov/pubmed/28280564
http://dx.doi.org/10.1098/rsos.160646
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author Okhovat, M.
Maguire, S. M.
Phelps, S. M.
author_facet Okhovat, M.
Maguire, S. M.
Phelps, S. M.
author_sort Okhovat, M.
collection PubMed
description 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 of avpr1a in the retrosplenial cortex, a brain region implicated in male space use and sexual fidelity. We find dramatic variation in methylation across the avrp1a locus, with pronounced diversity near the exon–intron boundary and in a genetically variable putative enhancer within the intron. Among our wild voles, differences in cortical avpr1a expression 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.
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spelling pubmed-53193302017-03-09 Methylation of avpr1a in the cortex of wild prairie voles: effects of CpG position and polymorphism Okhovat, M. Maguire, S. M. Phelps, S. M. R Soc Open Sci Biology (Whole Organism) 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 of avpr1a in the retrosplenial cortex, a brain region implicated in male space use and sexual fidelity. We find dramatic variation in methylation across the avrp1a locus, with pronounced diversity near the exon–intron boundary and in a genetically variable putative enhancer within the intron. Among our wild voles, differences in cortical avpr1a expression 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. The Royal Society Publishing 2017-01-18 /pmc/articles/PMC5319330/ /pubmed/28280564 http://dx.doi.org/10.1098/rsos.160646 Text en © 2017 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Biology (Whole Organism)
Okhovat, M.
Maguire, S. M.
Phelps, S. M.
Methylation of avpr1a in the cortex of wild prairie voles: effects of CpG position and polymorphism
title Methylation of avpr1a in the cortex of wild prairie voles: effects of CpG position and polymorphism
title_full Methylation of avpr1a in the cortex of wild prairie voles: effects of CpG position and polymorphism
title_fullStr Methylation of avpr1a in the cortex of wild prairie voles: effects of CpG position and polymorphism
title_full_unstemmed Methylation of avpr1a in the cortex of wild prairie voles: effects of CpG position and polymorphism
title_short Methylation of avpr1a in the cortex of wild prairie voles: effects of CpG position and polymorphism
title_sort methylation of avpr1a in the cortex of wild prairie voles: effects of cpg position and polymorphism
topic Biology (Whole Organism)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319330/
https://www.ncbi.nlm.nih.gov/pubmed/28280564
http://dx.doi.org/10.1098/rsos.160646
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