Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387614894> ?p ?o ?g. }
Showing items 1 to 57 of
57
with 100 items per page.
- W4387614894 abstract "Neuronal and behavioral adaptations to novel stimuli are regulated by temporally dynamic waves of transcriptional activity, which shape neuronal function and guide enduring plasticity. Neuronal activation promotes expression of an immediate early gene (IEG) program comprised primarily of activity-dependent transcription factors, which are thought to regulate a second set of late response genes (LRGs). However, while the mechanisms governing IEG activation have been well studied, the molecular interplay between IEGs and LRGs remain poorly characterized. Here, we used transcriptomic and chromatin accessibility profiling to define activity-driven responses in rat striatal neurons. As expected, neuronal depolarization generated robust changes in gene expression, with early changes (1 h) enriched for inducible transcription factors and later changes (4 h) enriched for neuropeptides, synaptic proteins, and ion channels. Remarkably, while depolarization did not induce chromatin remodeling after 1 h, we found broad increases in chromatin accessibility at thousands of sites in the genome at 4 h after neuronal stimulation. These putative regulatory elements were found almost exclusively at non-coding regions of the genome, and harbored consensus motifs for numerous activity-dependent transcription factors such as AP-1. Furthermore, blocking protein synthesis prevented activity-dependent chromatin remodeling, suggesting that IEG proteins are required for this process. Targeted analysis of LRG loci identified a putative enhancer upstream of Pdyn (prodynorphin), a gene encoding an opioid neuropeptide implicated in motivated behavior and neuro-psychiatric disease states. CRISPR-based functional assays demonstrated that this enhancer is both necessary and sufficient for Pdyn transcription. This regulatory element is also conserved at the human PDYN locus, where its activation is sufficient to drive PDYN transcription in human cells. These results suggest that IEGs participate in chromatin remodeling at enhancers and identify a conserved enhancer that may act as a therapeutic target for brain disorders involving dysregulation of Pdyn." @default.
- W4387614894 created "2023-10-14" @default.
- W4387614894 date "2023-10-13" @default.
- W4387614894 modified "2023-10-14" @default.
- W4387614894 title "Author response: Temporally specific gene expression and chromatin remodeling programs regulate a conserved Pdyn enhancer" @default.
- W4387614894 doi "https://doi.org/10.7554/elife.89993.2.sa4" @default.
- W4387614894 hasPublicationYear "2023" @default.
- W4387614894 type Work @default.
- W4387614894 citedByCount "0" @default.
- W4387614894 crossrefType "peer-review" @default.
- W4387614894 hasBestOaLocation W43876148941 @default.
- W4387614894 hasConcept C104317684 @default.
- W4387614894 hasConcept C111936080 @default.
- W4387614894 hasConcept C138885662 @default.
- W4387614894 hasConcept C150194340 @default.
- W4387614894 hasConcept C165864922 @default.
- W4387614894 hasConcept C167227067 @default.
- W4387614894 hasConcept C169760540 @default.
- W4387614894 hasConcept C179926584 @default.
- W4387614894 hasConcept C41895202 @default.
- W4387614894 hasConcept C54355233 @default.
- W4387614894 hasConcept C74254510 @default.
- W4387614894 hasConcept C83640560 @default.
- W4387614894 hasConcept C86339819 @default.
- W4387614894 hasConcept C86803240 @default.
- W4387614894 hasConcept C95444343 @default.
- W4387614894 hasConceptScore W4387614894C104317684 @default.
- W4387614894 hasConceptScore W4387614894C111936080 @default.
- W4387614894 hasConceptScore W4387614894C138885662 @default.
- W4387614894 hasConceptScore W4387614894C150194340 @default.
- W4387614894 hasConceptScore W4387614894C165864922 @default.
- W4387614894 hasConceptScore W4387614894C167227067 @default.
- W4387614894 hasConceptScore W4387614894C169760540 @default.
- W4387614894 hasConceptScore W4387614894C179926584 @default.
- W4387614894 hasConceptScore W4387614894C41895202 @default.
- W4387614894 hasConceptScore W4387614894C54355233 @default.
- W4387614894 hasConceptScore W4387614894C74254510 @default.
- W4387614894 hasConceptScore W4387614894C83640560 @default.
- W4387614894 hasConceptScore W4387614894C86339819 @default.
- W4387614894 hasConceptScore W4387614894C86803240 @default.
- W4387614894 hasConceptScore W4387614894C95444343 @default.
- W4387614894 hasLocation W43876148941 @default.
- W4387614894 hasOpenAccess W4387614894 @default.
- W4387614894 hasPrimaryLocation W43876148941 @default.
- W4387614894 hasRelatedWork W2023670712 @default.
- W4387614894 hasRelatedWork W2090160141 @default.
- W4387614894 hasRelatedWork W2118937292 @default.
- W4387614894 hasRelatedWork W2152611630 @default.
- W4387614894 hasRelatedWork W2688223077 @default.
- W4387614894 hasRelatedWork W2891762942 @default.
- W4387614894 hasRelatedWork W2992086063 @default.
- W4387614894 hasRelatedWork W3038565614 @default.
- W4387614894 hasRelatedWork W3145419749 @default.
- W4387614894 hasRelatedWork W3159317682 @default.
- W4387614894 isParatext "false" @default.
- W4387614894 isRetracted "false" @default.
- W4387614894 workType "peer-review" @default.