ArticleProceedings of the National Academy of Sciences of the United States of America2016
Stress-induced gene expression and behavior are controlled by DNA methylation and methyl donor availability in the dentate gyrus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 117 citations in OpenAlex.
- S-adenosylmethionine as an epigenetic treatment of depression in adults with childhood trauma.Epigenomics · 2026Trial
- Decitabine-induced DNA methylation remodeling reveals targetable biological processes in gilthead seabream pituitary and liver explants.Epigenetics · 2025Article
- The role of small extracellular vesicles in post-traumatic stress disorder.Global medical genetics · 2025Review
- Developmental Behavioural Plasticity and DNA Methylation Patterns in Response to Predation Stress in Trinidadian Guppies.Molecular ecology · 2025Article
- Poly ADP-ribosylation regulates Arc expression and promotes adaptive stress-coping.Psychopharmacology · 2025Article
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
- Unveiling the mechanistic nexus: how micronutrient enrichment shapes brain function, and cognitive health.Frontiers in molecular biosciences · 2025Review
- Stress-induced c-fos expression in the medial prefrontal cortex differentially affects the main residing cell phenotypes.Heliyon · 2024Article
- Emerging Roles of Vitamin BInternational journal of molecular sciences · 2024Review
- Epigenetics, Nutrition, and the Brain: Improving Mental Health through Diet.International journal of molecular sciences · 2024Review
- The cortisol switch between vulnerability and resilience.Molecular psychiatry · 2024Review
- Coping with the multifaceted and multifunctional role of cortisol in the brain.Neuroscience applied · 2024Review
- A decrease in NR2B expression mediated by DNA hypermethylation induces perioperative neurocognitive disorder in aged mice.CNS neuroscience & therapeutics · 2023Article
- Prenatal stress modulates HPA axis homeostasis of offspring through dentate TERT independently of glucocorticoids receptor.Molecular psychiatry · 2023Article
- Cognitive and Emotional Symptoms Induced by Chronic Stress Are Regulated by EGR1 in a Subpopulation of Hippocampal Pyramidal Neurons.International journal of molecular sciences · 2023Article
- Pilot Study of the Long-Term Effects of Radiofrequency Electromagnetic Radiation Exposure on the Mouse Brain.International journal of environmental research and public health · 2023Article
- Methyl Donors, Epigenetic Alterations, and Brain Health: Understanding the Connection.International journal of molecular sciences · 2023Review
- Protection of c-Fos from autophagic degradation by PRMT1-mediated methylation fosters gastric tumorigenesis.International journal of biological sciences · 2023Article
- Article
- No evidence for intervention-associated DNA methylation changes in monocytes of patients with posttraumatic stress disorder.Scientific reports · 2022Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
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Abstract
Stressful events evoke long-term changes in behavioral responses; however, the underlying mechanisms in the brain are not well understood. Previous work has shown that epigenetic changes and immediate-early gene (IEG) induction in stress-activated dentate gyrus (DG) granule neurons play a crucial role in these behavioral responses. Here, we show that an acute stressful challenge [i.e., forced swimming (FS)] results in DNA demethylation at specific CpG (5'-cytosine-phosphate-guanine-3') sites close to the c-Fos (FBJ murine osteosarcoma viral oncogene homolog) transcriptional start site and within the gene promoter region of Egr-1 (early growth response protein 1) specifically in the DG. Administration of the (endogenous) methyl donor S-adenosyl methionine (SAM) did not affect CpG methylation and IEG gene expression at baseline. However, administration of SAM before the FS challenge resulted in an enhanced CpG methylation at the IEG loci and suppression of IEG induction specifically in the DG and an impaired behavioral immobility response 24 h later. The stressor also specifically increased the expression of the de novo DNA methyltransferase Dnmt3a [DNA (cytosine-5-)-methyltransferase 3 alpha] in this hippocampus region. Moreover, stress resulted in an increased association of Dnmt3a enzyme with the affected CpG loci within the IEG genes. No effects of SAM were observed on stress-evoked histone modifications, including H3S10p-K14ac (histone H3, phosphorylated serine 10 and acetylated lysine-14), H3K4me3 (histone H3, trimethylated lysine-4), H3K9me3 (histone H3, trimethylated lysine-9), and H3K27me3 (histone H3, trimethylated lysine-27). We conclude that the DNA methylation status of IEGs plays a crucial role in FS-induced IEG induction in DG granule neurons and associated behavioral responses. In addition, the concentration of available methyl donor, possibly in conjunction with Dnmt3a, is critical for the responsiveness of dentate neurons to environmental stimuli in terms of gene expression and behavior.
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