ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Setdb1 histone methyltransferase regulates mood-related behaviors and expression of the NMDA receptor subunit NR2B.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 114 citations in OpenAlex.
- Gingival Response to Dental Implant: Comparison Study on the Effects of New Nanopored Laser-Treated vs. Traditional Healing Abutments.International journal of molecular sciences · 2020Trial
- SETDB1 modulates neuroinflammation in the mouse cortex by regulating neuronal P2rx7 expression.Molecular psychiatry · 2026Article
- Targeted neuronal reprogramming rescues memory and neural synchrony in Alzheimer's disease.Molecular biomedicine · 2026Article
- Histone Modifications in Psychiatry: From Canonical Marks to Neurotransmitter-Mediated Epigenetic Signatures.Alpha psychiatry · 2026Review
- DNA methylation and the opposing NMDAR dysfunction in schizophrenia and major depression disorders: a converging model for the therapeutic effects of psychedelic compounds in the treatment of psychiatric illness.Molecular psychiatry · 2023Review
- Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential.Signal transduction and targeted therapy · 2023Review
- Histone methyltransferase SETDB1 promotes osteogenic differentiation in osteoporosis by activating OTX2-mediated BMP-Smad and Wnt/β-catenin pathways.Human cell · 2023Article
- Physiological and cognitive changes after treatments of cyclophosphamide, methotrexate, and fluorouracil: implications of the gut microbiome and depressive-like behavior.Frontiers in neuroscience · 2023Article
- The Changes of Histone Methylation Induced by Adolescent Social Stress Regulate the Resting-State Activity in mPFC.Research (Washington, D.C.) · 2023Article
- SETDB1 regulates microtubule dynamics.Cell proliferation · 2022Article
- Establishment of H3K9-methylated heterochromatin and its functions in tissue differentiation and maintenance.Nature reviews. Molecular cell biology · 2022Review
- The GluN2B-Trp373 NMDA Receptor Variant is Associated with Autism-, Epilepsy-Related Phenotypes and Reduces NMDA Receptor Currents in Rats.Neurochemical research · 2022Article
- Physical-Exercise-Induced Antioxidant Effects on the Brain and Skeletal Muscle.Antioxidants (Basel, Switzerland) · 2022Review
- Effects of Histone Modification in Major Depressive Disorder.Current neuropharmacology · 2022Review
- Structure, Activity and Function of the SETDB1 Protein Methyltransferase.Life (Basel, Switzerland) · 2021Review
- Temporarily Epigenetic Repression in Bergmann Glia Regulates the Migration of Granule Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- The emerging role of chromatin remodelers in neurodevelopmental disorders: a developmental perspective.Cellular and molecular life sciences : CMLS · 2021Review
- Epigenetic Neuropharmacology: Drugs Affecting the Epigenome in the Brain.Annual review of pharmacology and toxicology · 2021Review
- Neuroinflammatory Basis of Depression: Learning From Experimental Models.Frontiers in cellular neuroscience · 2021Review
- Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy.Frontiers in molecular neuroscience · 2021Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Histone methyltransferases specific for the histone H3-lysine 9 residue, including Setdb1 (Set domain, bifurcated 1)/Eset/Kmt1e are associated with repressive chromatin remodeling and expressed in adult brain, but potential effects on neuronal function and behavior remain unexplored. Here, we report that transgenic mice with increased Setdb1 expression in adult forebrain neurons show antidepressant-like phenotypes in behavioral paradigms for anhedonia, despair, and learned helplessness. Chromatin immunoprecipitation in conjunction with DNA tiling arrays (ChIP-chip) revealed that genomic occupancies of neuronal Setdb1 are limited to <1% of annotated genes, which include the NMDA receptor subunit NR2B/Grin2B and other ionotropic glutamate receptor genes. Chromatin conformation capture and Setdb1-ChIP revealed a loop formation tethering the NR2B/Grin2b promoter to the Setdb1 target site positioned 30 kb downstream of the transcription start site. In hippocampus and ventral striatum, two key structures in the neuronal circuitry regulating mood-related behaviors, Setdb1-mediated repressive histone methylation at NR2B/Grin2b was associated with decreased NR2B expression and EPSP insensitivity to pharmacological blockade of NR2B, and accelerated NMDA receptor desensitization consistent with a shift in NR2A/B subunit ratios. In wild-type mice, systemic treatment with the NR2B antagonist, Ro25-6981 [R-(R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propranol], and hippocampal small interfering RNA-mediated NR2B/Grin2b knockdown resulted in behavioral changes similar to those elicited by the Setdb1 transgene. Together, these findings point to a role for neuronal Setdb1 in the regulation of affective and motivational behaviors through repressive chromatin remodeling at a select set of target genes, resulting in altered NMDA receptor subunit composition and other molecular adaptations.
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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.