Chronic social stress induces DNA methylation changes at an evolutionary conserved intergenic region in chromosome X

Abstract

Chronic stress resulting from prolonged exposure to negative life events increases the risk of mood and anxiety disorders. Although chronic stress can change gene expression relevant for behavior, molecular regulators of this change have not been fully determined. One process that could play a role is DNA methylation, an epigenetic process whereby a methyl group is added onto nucleotides, predominantly cytosine in the CpG context, and which can be induced by chronic stress. It is unknown to what extent chronic social defeat, a model of human social stress, influences DNA methylation patterns across the genome. Our study addressed this question by using a targeted-capture approach called Methyl-Seq to investigate DNA methylation patterns of the dentate gyrus at putative regulatory regions across the mouse genome from mice exposed to 14 days of social defeat. Findings were replicated in independent cohorts by bisulfite-pyrosequencing. Two differentially methylated regions (DMRs) were identified. One DMR was located at intron 9 of Drosha, and it showed reduced methylation in stressed mice. This observation replicated in one of two independent cohorts. A second DMR was identified at an intergenic region of chromosome X, and methylation in this region was increased in stressed mice. This methylation difference replicated in two independent cohorts and in Major Depressive Disorder (MDD) postmortem brains. These results highlight a region not previously known to be differentially methylated by chronic social defeat stress and which may be involved in MDD.

Hepatic DNA Methylation in Response to Early Stimulation of Microbiota with Lactobacillus Synbiotics in Broiler Chickens

“…DNA methylation mostly silences gene expression, which is defined as epigenetic modification of gene expression. The process of DNA methylation can be modulated by environmental factors such as nutrition [1], stress [2], climate and intestinal microbiota [3]. Crosstalk between microbiome and host metabolism often leads to epigenetic regulation of gene expression [4].…”

Amygdala 5-HTT Gene Network Moderates the Effects of Postnatal Adversity on Attention Problems: Anatomo-Functional Correlation and Epigenetic Changes

“…Studies have been using p-ICA to correlate biological pathways with variations in gray matter density, which represents an important tool to identify an anatomical-functional basis for a behavioral phenotype (Khadka et al, 2016;Miguel et al, 2019). Additionally, stressors in early life are known to alter the expression of genes and cellular processes that influence behavior, and one of the molecular processes that contributes to this change is DNA methylation (Vinkers et al, 2015;Hing et al, 2018). However, the mechanisms linking these associations need to be further investigated.…”

Oxidative and Epigenetic Changes and Gut Permeability Response in Early-Treated Chickens with Antibiotic or Probiotic

“…DNA methylation is an epigenetic mechanism that inhibits DNA transcription through the addition of methyl residues to cysteine. DNA methylation can be modulated by environmental factors such as diet, stress, climate, and the gut microbiota [23,[45][46][47]. Literature data show that the level of DNA methylation may be influenced by the short-chain fatty acid butyrate, which is a product of prebiotic fermentation [48,49].…”