RT Journal Article
SR Electronic
T1 Regions with intermediate DNA methylation are epigenomic hotspots governing behavioral adaptation to changing environments
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.12.11.519758
DO 10.1101/2022.12.11.519758
A1 Elizabeth Brindley
A1 Faten Taki
A1 Shannon C. Odell
A1 Madelyn R Baker
A1 Judit Gal Toth
A1 Miklos Toth
YR 2022
UL http://biorxiv.org/content/early/2022/12/11/2022.12.11.519758.abstract
AB Epigenetic and associated gene expression changes in the brain drive animals’ ability to adapt to changing environments. However, epigenetic attributes of environmental adaptation are unknown. Here we show that exercise, unpredictable stress, and environmental enrichment, conditions that elicit adaptive changes in synaptic plasticity and spatial learning, result in CpG methylation changes in regions that exist in both methylated and unmethylated states (i.e., epigenetically bistable) in hippocampal granule cells. Sustained exposures altered both the epiallelic proportions at these regions and neuronal and behavioral adaptation, indicating their adaptive nature. These malleable regions were enriched in exons and enhancer-associated chromatin marks. Their locations were mostly unique to specific environments but converged on similar synaptic genes. Lastly, manipulating DNA methylation altered epiallelic proportions at bistable regions in granule cells and phenocopied adaptive behavior. We propose that shifts in epiallelic proportions at evolutionarily conserved bistable regions, via gene expression changes, contribute to hippocampal plasticity and behavioral adaptation to changing environments.Competing Interest StatementThe authors have declared no competing interest.