ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018
Cell-Type-Specific Epigenetic Editing at the Fosb Gene Controls Susceptibility to Social Defeat Stress.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 104 citations in OpenAlex.
- Review
- Transposable Elements Are Dynamically Regulated in Medium Spiny Neurons and May Contribute to the Molecular and Behavioral Adaptations to Cocaine.Biological psychiatry · 2026Article
- The influence of HINT1 protein in nucleus accumbens on aggressive behavior and anxiety-like behavior.Psychopharmacology · 2026Article
- ∆FOSB in the Nucleus Accumbens Core Is Required for Increased Anxiety, but Not Decreased Social Motivation, Following Estrogen Withdrawal in Female Mice.Genes, brain, and behavior · 2026Article
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Derepression of transposable elements in the mouse prefrontal cortex disrupts social behavior.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Epigenetic editing of Cartpt promotes acquisition and extinction of cocaine memory.bioRxiv : the preprint server for biology · 2025Article
- ΔFOSB in the nucleus accumbens core is required for increased anxiety, but not decreased social motivation, following estrogen withdrawal in female mice.bioRxiv : the preprint server for biology · 2025Article
- How dopamine guides our social world.Pharmacological reviews · 2025Review
- Emerging Trends and Hot Spots in Epigenetic Modifications in Neurology: A Bibliometric Analysis.Molecular neurobiology · 2025Review
- The function of the ZFP189 transcription factor in the nucleus accumbens facilitates cocaine-specific transcriptional and behavioral adaptations.Molecular psychiatry · 2025Article
- A review of the effects of different types of social behaviors on the recruitment of neuropeptides and neurotransmitters in the nucleus accumbens.Frontiers in neuroendocrinology · 2025Review
- The Promise of Epigenetic Editing for Treating Brain Disorders.Sub-cellular biochemistry · 2025Review
- The effects of different types of social interactions on the electrophysiology of neurons in the nucleus accumbens in rodents.Neuroscience and biobehavioral reviews · 2024Review
- Precision epigenetic editing: Technological advances, enduring challenges, and therapeutic applications.Cell chemical biology · 2024Review
- Cell- and Pathway-Specific Disruptions in the Accumbens of Fragile X Mouse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Neurobiology and systems biology of stress resilience.Physiological reviews · 2024Review
- Neurobiological basis of stress resilience.Neuron · 2024Review
- Histone serotonylation in dorsal raphe nucleus contributes to stress- and antidepressant-mediated gene expression and behavior.Nature communications · 2024Article
- Identification of stress-induced epigenetic methylation onto dopamine D2 gene and neurological and behavioral consequences.Gene & protein in disease · 2024Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Chronic social defeat stress regulates the expression of Fosb in the nucleus accumbens (NAc) to promote the cell-type-specific accumulation of ΔFosB in the two medium spiny neuron (MSN) subtypes in this region. ΔFosB is selectively induced in D1-MSNs in the NAc of resilient mice, and in D2-MSNs of susceptible mice. However, little is known about the consequences of such selective induction, particularly in D2-MSNs. This study examined how cell-type-specific control of the endogenous Fosb gene in NAc regulates susceptibility to social defeat stress. Histone post-translational modifications (HPTMs) were targeted specifically to Fosb using engineered zinc-finger proteins (ZFPs). Fosb-ZFPs were fused to either the transcriptional repressor, G9a, which promotes histone methylation or the transcriptional activator, p65, which promotes histone acetylation. These ZFPs were expressed in D1- vs D2-MSNs using Cre-dependent viral expression in the NAc of mice transgenic for Cre recombinase in these MSN subtypes. We found that stress susceptibility is oppositely regulated by the specific cell type and HPTM targeted. We report that Fosb-targeted histone acetylation in D2-MSNs or histone methylation in D1-MSNs promotes a stress-susceptible, depressive-like phenotype, while histone methylation in D2-MSNs or histone acetylation in D1-MSNs increases resilience to social stress as quantified by social interaction behavior and sucrose preference. This work presents the first demonstration of cell- and gene-specific targeting of histone modifications, which model naturally occurring transcriptional phenomena that control social defeat stress behavior. This epigenetic-editing approach, which recapitulates physiological changes in gene expression, reveals clear differences in the social defeat phenotype induced by Fosb gene manipulation in MSN subtypes.
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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.