ArticleProceedings of the National Academy of Sciences of the United States of America2014
FGF2 is a target and a trigger of epigenetic mechanisms associated with differences in emotionality: partnership with H3K9me3.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Genetic Liability for Internalizing Versus Externalizing Behavior Manifests in the Developing and Adult Hippocampus: Insight From a Meta-analysis of Transcriptional Profiling Studies in a Selectively Bred Rat Model.Biological psychiatry · 2021Pooled it
- Epigenetic editing of marine medaka (Zoological research · 2026Article
- Environmental enrichment and physical exercise prevent stress-induced social avoidance and blood-brain barrier alterations via Fgf2.Nature communications · 2026Article
- mScience China. Life sciences · 2025Article
- The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review.eNeuro · 2023Review
- Role of microRNAs and long non‑coding RNAs in glucocorticoid signaling (Review).International journal of molecular medicine · 2022Review
- Review
- Differences in microglia morphological profiles reflect divergent emotional temperaments: insights from a selective breeding model.Translational psychiatry · 2022Article
- Adolescent cocaine differentially impacts psychomotor sensitization and epigenetic profiles in adult male rats with divergent affective phenotypes.Frontiers in psychiatry · 2022Article
- Fibroblast Growth Factor Signalling in the Diseased Nervous System.Molecular neurobiology · 2021Review
- Computational Analysis of Multidimensional Behavioral Alterations After Chronic Social Defeat Stress.Biological psychiatry · 2021Article
- Unexpected Transcriptional Programs Contribute to Hippocampal Memory Deficits and Neuronal Stunting after Early-Life Adversity.Cell reports · 2020Article
- Revisiting the Stress Concept: Implications for Affective Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Review
- Unraveling the epigenetic landscape of depression: focus on early life stress .Dialogues in clinical neuroscience · 2019Review
- Adaptation to single housing is dynamic: Changes in hormone levels, gene expression, signaling in the brain, and anxiety-like behavior in adult male C57Bl/6J mice.Hormones and behavior · 2019Article
- Effects of early-life FGF2 on ultrasonic vocalizations (USVs) and the mu-opioid receptor in male Sprague-Dawley rats selectively-bred for differences in their response to novelty.Brain research · 2019Article
- Epigenetic Mechanisms Within the Cingulate Cortex Regulate Innate Anxiety-Like Behavior.The international journal of neuropsychopharmacology · 2019Article
- Understanding Addiction Using Animal Models.Frontiers in behavioral neuroscience · 2019Article
- Selectively Bred Rats Provide a Unique Model of Vulnerability to PTSD-Like Behavior and Respond Differentially to FGF2 Augmentation Early in Life.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- Utilizing a unique animal model to better understand human temperament.Current opinion in behavioral sciences · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Posttranslational modifications of histone tails in chromatin template can result from environmental experiences such as stress and substance abuse. However, the role of epigenetic modifications as potential predisposing factors in affective behavior is less well established. To address this question, we used our selectively bred lines of high responder (bHR) and low responder (bLR) rats that show profound and stable differences in affective responses, with bLRs being prone to anxiety- and depression-like behavior and bHRs prone to addictive behavior. We first asked whether these phenotypes are associated with basal differences in epigenetic profiles. Our results reveal broad between-group differences in basal levels of trimethylated histone protein H3 at lysine 9 (H3K9me3) in hippocampus (HC), amygdala, and nucleus accumbens. Moreover, levels of association of H3K9me3 at Glucocorticoid Receptor (GR) and Fibroblast growth Factor 2 (FGF2) promoters differ reciprocally between bHRs and bLRs in these regions, consistent with these genes' opposing levels of expression and roles in modulating anxiety behavior. Importantly, this basal epigenetic pattern is modifiable by FGF2, a factor that modulates anxiety behavior. Thus, early-life FGF2, which decreases anxiety, altered the levels of H3K9me3 and its binding at FGF2 and GR promoters of bLRs rendering them more similar to bHRs. Conversely, knockdown of HC FGF2 altered both anxiety behavior and levels of H3K9me3 in bHRs, rendering them more bLR-like. These findings implicate FGF2 as a modifier of epigenetic mechanisms associated with emotional responsiveness, and point to H3K9me3 as a key player in the regulation of affective vulnerability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.