Arnt2 tunes activity-dependent gene expression through NCoR2-mediated repression and Npas4-mediated activation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA498055 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:ChIP-, ATAC-, and RNA-seq data Neuronal activity-dependent transcription is tuned to ensure precise gene induction during periods of heightened synaptic activity, allowing for appropriate responses of activated neurons within neural circuits. The consequences of aberrant induction of activity-dependent genes on neuronal physiology are not yet clear. Here, we demonstrate that, in the absence of synaptic excitation, the basic-helix-loop-helix (bHLH)-PAS family transcription factor ARNT2 recruits the NCoR2 co-repressor complex to suppress neuronal activity-dependent regulatory elements and maintain low basal levels of inducible genes. This restricts inhibition of excitatory neurons, maintaining them in a state that is receptive to future sensory stimuli. By contrast, in response to heightened neuronal activity, ARNT2 recruits the neuronal-specific bHLH-PAS factor NPAS4 to activity-dependent regulatory elements to induce transcription and thereby increase somatic inhibitory input. Thus, the interplay of bHLH-PAS complexes at activity-dependent regulatory elements maintains temporal control of activity-dependent gene expression and scales somatic inhibition with circuit activity.
2019-04-11 | GSE121660 | GEO
Project description: Not available
| S-EPMC6504996 | biostudies-literature
Project description:We identify pathways regulated by Ncor2 in astrocytes during EAE
2023-02-08 | GSE198971 | GEO
Project description:we performed a DNA microarray experiment to identify activity-regulated genes that are misregulated in the absence of Npas4. Keywords: Primary neuron culture, depolarization, activity-dependent, Npas4
2008-09-24 | GSE11258 | GEO
Project description:We performed a DNA microarray experiment to identify activity-regulated genes that are misregulated in the absence of Npas4. Experiment Overall Design: We infected mouse hippocampal neurons with lentivirus expressing Npas4-RNAi or control-RNAi @ 3 DIV and depolarized the neurons @ 8 DIV with 50 mM of KCl for 0, 1, 3 or 6 hours. Neurons were lysed, mRNA isolated and hybridized to Affymetrix arrays. Data were collected from 3 independent experiments.
2008-10-26 | E-GEOD-11258 | biostudies-arrayexpress
Project description:Chronic social defeat stress induces anhedonia-like behavior deficits. We demonstrated that mPFC NPAS is requred for chronic social defeat stress-induced deficits in the sucrose preference and effort-based reward seeking behavior. We conducted the RNA-seq analysis for differential expression genes in the mouse mPFC samples of AAV-mediated Npas4 shRNA expression tissue.
2023-02-10 | GSE165586 | GEO
Project description:Neuronal activity is critical for adaptive circuit remodeling but poses an inherent risk to the stability of the genome across the long lifespan of post-mitotic neurons1-5. Whether neurons have acquired specialized genome protection mechanisms that enable them to withstand decades of potentially damaging stimuli during periods of heightened activity is not known. Here we identify an activity-dependent DNA repair mechanism via a new form of the NuA4/TIP60 chromatin modifier that assembles in activated neurons around the inducible, neuronal-specific transcription factor NPAS4. We purify this complex directly from the brain and demonstrate its functions in eliciting activity-dependent changes to neuronal transcriptomes and circuitry. By identifying the landscape of activity-induced DNA double-strand breaks in the brain, we show that the NPAS4:NuA4 complex binds to recurrently damaged regulatory elements and recruits additional DNA repair machinery to stimulate their repair. Gene regulatory elements bound by the NPAS4:NuA4 complex are partially protected from age-dependent accumulation of somatic mutations. Impaired NPAS4:NuA4 signaling leads to a cascade of cellular defects including dysregulated transcriptional responses to activity, loss of control over neuronal inhibition, and genome instability, culminating in reduced organismal lifespan. In addition, mutations in several components of the NuA4 complex are reported to lead to neurodevelopmental disorders and autism. Together, these findings identify a neuronal-specific complex that couples neuronal activity directly to genome preservation and whose disruption may contribute to developmental disorders, neurodegeneration and aging.
2023-02-15 | PXD038718 | Pride
Project description:To identify the activity-induced gene expression programs in inhibitory and excitatory neurons, we analyzed RNA extracted from cultured E14 mouse MGE- and CTX-derived neurons (DIV 10) after these cultures were membrane-depolarized for 0, 1 and 6 hrs with 55mM extracellular KCl. To identify the gene programs regulated in these cells by the activity-induced early-response transcription factor Npas4, we repeated the same experiment in the MGE- and CTX-cultures lacking Npas4 (Npas4-KO). Littermate mouse E14 MGE- or CTX-derived neurons (WT or KO for Npas4) were cultured for 9 days, quieted overnight with TTX and AP-5 and then membrane-depolarized for 0, 1 or 6 hours by raising the extracellular KCl-concentration to 55mM. RNA was then extracted and analyzed using Affymetrix GeneChip Mouse Expression Set 430 2.0 microarray platform.
2015-06-04 | E-GEOD-55588 | biostudies-arrayexpress
Project description:Use of addictive substances often creates powerful and enduring associations with external cues that act as relapse triggers in individuals recovering from a substance use disorder (SUD). In the reward-associated brain region, the nucleus accumbens (NAc), drug use or drug-associated cue exposure activates a subset of D1 dopamine receptor-expressing medium spiny neurons (D1-MSNs), which typically promotes drug seeking, and a smaller subset of D2 dopamine receptor-expressing MSNs (D2-MSNs), which typically opposes drug seeking. The activity-regulated transcription factor, Neuronal PAS Domain Protein 4 (NPAS4), is activated in a small subset of NAc neurons during cocaine conditioning, and NAc NPAS4 is required for drug-context memories. Using a new Npas4-TRAP mouse combined with chemogenetics, we found that the during cocaine conditioning, the NPAS4-positive ensemble is required for drug-context associations. Single-cell transcriptomic analyses and in situ hybridization of NAc tissues from drug-conditioned mice revealed that NPAS4 is expressed predominantly in MSNs, and using cell type-specific molecular genetic approaches, we found that NPAS4 in D2-MSNs, but not D1-MSNs, was required for both drug-context associations and cue-reinstated cocaine seeking. Similarly, NPAS4 in NAc D2-MSNs, but not D1-MSNs, blocked cocaine experience-dependent strengthening of glutamatergic prefrontal cortical (PFC) inputs onto D2-MSNs. Analysis of differential gene expression in D2-MSNs revealed that NPAS4 and cocaine conditioning influence a gene expression program associated with synapses, dendrites, neuronal projections, dopamine, and cocaine. Together, our data reveal that NPAS4 functions during active cocaine use to maintain the imbalance of D1-MSN:D2-MSN activation and cue-induced drug seeking by suppressing excitatory drive onto relapse-opposing NAc D2-MSN circuits.
2023-08-31 | GSE210850 | GEO
Project description:Npas4 CUT&Tag dataset, Adult male WT C57BL/6J mice underwent discriminative fear conditioning and immediately injected saline. 90 minutes after fear conditioning, The amygdala tissue was extracted for further experiment. Npas4 CUT&Tag was performed to elucidate possible downstream targets which contributes regulation of fear expression during fear retreival.
2023-07-05 | GSE194069 | GEO