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Cited by 143Genomics and Chromatin DynamicsChromatin Remodeling and CancerNeuroscience and Neuropharmacology Research

Three-dimensional genome restructuring across timescales of activity-induced neuronal gene expression

Open access
Beagan, Jonathan A., Pastuzyn, Elissa D., Fernandez, Lindsey R., Guo, Michael H., Feng, Kelly, Titus, Katelyn R., Chandrashekar, Harshini, Shepherd, Jason D. +1 more·2020·Nature Neuroscience
DOI 10.1038/s41593-020-0634-6PMC PMC7558717
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Abstract

Neuronal activation induces rapid transcription of immediate early genes (IEGs) and longer-term chromatin remodeling around secondary response genes (SRGs). Here, we use high-resolution chromosome-conformation-capture carbon-copy sequencing (5C-seq) to elucidate the extent to which long-range chromatin loops are altered during short- and long-term changes in neural activity. We find that more than 10% of loops surrounding select IEGs, SRGs, and synaptic genes are induced de novo during cortical neuron activation. IEGs Fos and Arc connect to activity-dependent enhancers via singular short-range loops that form within 20 min after stimulation, prior to peak messenger RNA levels. By contrast, the SRG Bdnf engages in both pre-existing and activity-inducible loops that form within 1-6 h. We also show that common single-nucleotide variants that are associated with autism and schizophrenia are colocalized with distinct classes of activity-dependent, looped enhancers. Our data link architectural complexity to transcriptional kinetics and reveal the rapid timescale by which higher-order chromatin architecture reconfigures during neuronal stimulation.

AI snapshot

Written from the paper’s full text.

TL;DR

Using 5C-seq across activity states and time points in mouse cortical neurons, this study shows that neuronal activation rapidly reconfigures long-range chromatin loops around immediate early genes and slower secondary response genes. It links de novo versus pre-existing loop classes to distinct transcriptional kinetics and to schizophrenia- or autism-associated noncoding variants.

Key findings

  • Within 12.2 Mb queried around *Arc*, *Bdnf*, *Fos*, *Nrxn1*, *Syt1*, and *Nlgn3*, the authors detected 215 activity-invariant, 29 activity-induced, and 9 activity-decommissioned loops; more than 10% of loops surrounding select IEGs, SRGs, and synaptic genes were induced de novo.
  • Activity-induced loops anchored by activity-induced enhancers (class 1, n = 11) connected to genes with a 24-fold activity-dependent expression increase, whereas pre-existing loops anchored by activity-induced enhancers (class 2, n = 41) connected to genes with a 1.3-fold increase.
  • *Fos* and *Arc* formed singular short-range loops with activity-dependent enhancers that peaked by 20 min after stimulation, before peak mRNA at 60 min; *Bdnf* engaged in longer class 1 loops of 840 kb and 1,700 kb and class 2 loops that formed at 60–360 min, with maximum signal at 360 min.
  • Schizophrenia-associated noncoding SNVs (n = 80, P < 5 × 10−8) preferentially colocalized with class 3 loops anchored by activity-decommissioned enhancers, while autism-associated SNVs (n = 126, P < 10−4) colocalized with class 2 loops anchored by activity-inducible enhancers.

Methods

  • Primary murine cortical neurons were cultured for 15 days in vitro and treated for 24 h with 10 μM bicuculline, 1 μM tetrodotoxin, or left untreated; acute time-course experiments used 24 h TTX followed by 0, 5, 20, 60, or 360 min of bicuculline.
  • The authors generated high-resolution 5C-seq maps across 12.2 Mb around selected genes, plus H3K27ac ChIP–seq, total RNA-seq, and reanalyzed published mouse and human Hi-C data; loops were called with 3DeFDR and Hi-C loop-calling methods, and enhancer–gene links were modeled with an adapted activity-by-contact approach.
  • Disease-variant analyses used GWAS summary statistics for schizophrenia and autism spectrum disorders, SNP matching, Fisher’s exact tests, and LD score regression.

Limitations

  • The paper states that future functional dissection with genome editing is required to test whether disease-associated variants disrupt enhancers or loop structure, and that genome-wide Hi-C under diverse activity-induction conditions is needed to estimate class effects more precisely.
  • The paper notes that published Hi-C data represent only the untreated activity state, so activity-induced class 1 loops could not be assessed genome-wide; it also calls for future human activity-dependent loop maps.
  • Evident from the text: the main architectural findings come from an in vitro mouse cortical neuron system and 5C maps limited to 12.2 Mb around selected loci, and the disease-variant results are colocalization/enrichment analyses rather than causal tests.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41593-020-0634-6

Cites

71 of 71 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 22 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Class 3 loops showed strong and unchanged interaction frequency.

    “Activity-invariant loops anchored by activity-decommissioned enhancers showed a strong and unchanged interaction frequency (class 3, Fig. 3f).”
    Quote in the paperSubstantial claim
  • Findingown data

    The Fos and Arc loops form prior to peak mRNA levels.

    “IEGs Fos and Arc connect to activity-dependent enhancers via singular short-range loops that form within 20 min after stimulation, prior to peak messenger RNA levels.”
    Quote in the paperSubstantial claim
  • Findingown data

    Total sum interaction frequency made by each gene shows no correlation with gene expression.

    “whereas the total sum interaction frequency made by each gene showed no correlation with gene expression”
    Quote in the paperSubstantial claim
  • Findingown data

    Class 2 pre-existing loops connect genes involved in general cellular functions such as RNA processing to activity-induced enhancers.

    “Class 2 pre-existing loops connect genes involved in several general cellular functions such as RNA processing to activity-induced enhancers”
    Quote in the paperSubstantial claim
    • Rests on an assumption: H3K27ac signal correlates with enhancer and promoter activity.
  • Findingown data

    At enhancers connected through these loops to activity-upregulated genes, H3K27ac signal consistently increases.

    “as well as a consistent increase in H3K27ac signal at enhancers that connected through these loops to activity-upregulated genes”
    Quote in the paperSubstantial claim
    • Rests on an assumption: H3K27ac signal correlates with enhancer and promoter activity.
  • May combine two claims. 24
  • Classified as probably not a substantial claim. 21

  • May combine two claims.

    Findingown data

    The majority of differentially expressed genes in class 2 versus class 3 loops are upregulated and downregulated, respectively, due to activity.

    “The majority of differentially expressed genes in class 2 versus class 3 loops were upregulated and downregulated, respectively, due to activity”
    Quote in the paperSubstantial claim
    • Rests on an assumption: H3K27ac signal correlates with enhancer and promoter activity.

  • Classified as probably not a substantial claim.

    Findingown data

    Genome-wide loops were stratified into class 2 (n = 4,764) and class 3 (n = 3,259) groups.

    “stratify them into class 2 (n = 4,764) and class 3 (n = 3,259) groups”
    Quote in the paperSubstantial claim
    • Rests on an assumption: H3K27ac signal correlates with enhancer and promoter activity.

  • May combine two claims.

    Findingown data

    Immediate early genes in the 5C regions form simple short-range loops with activity-dependent enhancers and fall nearly exclusively in the class 1 category.

    “IEGs in our 5C regions form simple short-range loops with activity-dependent enhancers, and thus fall nearly exclusively in the class 1 category”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Within the 12.2 Mb queried, there are 215 activity-invariant, 29 activity-induced, and 9 activity-decommissioned loops.

    “resulting in the sensitive detection of 215 activity-invariant, 29 activity-induced, and 9 activity-decommissioned loops within the 12.2 Mb of the genome queried”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Specific genes involved in homeostatic plasticity, such as Gria1, are connected in class 3 loops to activity-decommissioned enhancers and are downregulated during chronic high activity.

    “we find that specific genes that are involved in homeostatic plasticity, such as Gria1, are connected in class 3 loops to activity-decommissioned enhancers and are downregulated during chronic high activity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    LD score regression confirmed a stronger enrichment of autism spectrum disorder-associated heritability in class 2 loop anchors than class 3, whereas schizophrenia heritability displayed the opposite trend.

    “Our LD score regression analysis confirmed a stronger enrichment of ASD-associated heritability in class 2 loop anchors than that for class 3, whereas heritability for schizophrenia displayed the opposite trend”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Finucane, H. K. et al. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat. Genet. 47, 1228–1235 (2015). source

      Not checked in the free run.

    • Rests on an assumption: Activity-dependent enhancer classes identified in mouse cortical neurons correspond to functionally equivalent regulatory elements in human brain.

  • May combine two claims.

    Findingown data

    Bdnf enhancers and expression were upregulated in parallel with loops and did not reach maximum signal until 360 min of stimulated activity.

    “Bdnf enhancers and expression were upregulated in parallel with loops and did not reach maximum signal in our time course until 360 min of stimulated activity”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Schizophrenia-associated SNVs are enriched at class 3 loops and are connected to downregulated genes after synaptic activity.

    “We also observe that schizophrenia-associated SNVs are enriched at class 3 loops and are connected to downregulated genes after synaptic activity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Bdnf loops include at least two class 1 activity-induced loops anchored by activity-induced enhancers, spanning 840 kb and 1,700 kb.

    “at least two class 1 activity-induced loops anchored by activity-induced enhancers, but spanning longer distances (840 kb and 1,700 kb) than those formed with IEGs”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Bdnf loops preferentially target its first promoter, from which the highest transcription and strongest upregulation after 24 h Bic-induced neuronal activation were observed.

    “The loops formed by Bdnf preferentially targeted its first promoter, from which we observed the highest level of transcription and strongest upregulation after 24 h of Bic-induced neuronal activation”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Foxp1 displays mouse-human conservation of local genome architecture and loops to several autism spectrum disorder-associated single-nucleotide variants and activity-induced enhancers.

    “Foxp1, which has been found previously to regulate brain development and synaptic plasticity44, displays remarkable mouse–human conservation of local genome architecture, and loops to several ASD-associated SNVs (Extended Data Fig. 10c) and activity-induced enhancers”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44] Araujo, D. J. et al. Foxp1 in forebrain pyramidal neurons controls gene expression required for spatial learning and synaptic plasticity. J. Neurosci. 37, 10917–10931 (2017). source

      Not checked in the free run.

    • Rests on an assumption: Activity-dependent enhancer classes identified in mouse cortical neurons correspond to functionally equivalent regulatory elements in human brain.

  • May combine two claims.

    Findingown data

    Enhancers that loop to both Fos and Arc peak in activity 20 min after neuronal activity and exhibit lower activity at all other time points.

    “The enhancers that loop to both Fos and Arc peak in activity 20 min after neuronal activity, and exhibit lower activity at all other time points”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Class 1 and class 2 loops connect to genes exhibiting a 24- and 1.3-fold activity-dependent increase in expression, respectively.

    “Class 1 and class 2 loops connect to genes exhibiting a 24- and 1.3-fold activity-dependent increase in expression, respectively.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: H3K27ac signal correlates with enhancer and promoter activity.

  • Classified as probably not a substantial claim.

    Findingown data

    25,722 background loops were identified as Hi-C contact matrix entries with P > 0.99 and interaction frequency > 0 in both cortical plate and germinal zone data sets.

    “In addition, 25,722 ‘background loops’ were identified as those Hi-C contact matrix entries that had a P value of >0.99 and an interaction frequency count of >0 in both cortical plate and germinal zone data sets.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    There were 2,139 Class 2 genes.

    “N = 2139 Class 2 genes”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingcitation

    Merging cortical plate and germinal zone loops created a master set of 24,544 loops spanning the two brain tissues.

    “Cortical plate and germinal zone loops were then merged to create a master set of 24,544 loops spanning the two brain tissues.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Won, H. et al. Chromosome conformation elucidates regulatory relationships in developing human brain. Nature 538, 523–527 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    5C maps from mature primary cortical neurons are highly correlated with and exhibit similar loops as published Hi-C maps from ES cell-derived cortical neurons.

    “5C maps from our mature primary cortical neurons were highly correlated with and exhibited similar loops as published Hi-C maps from ES cell-derived cortical neurons”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Bonev, B. et al. Multiscale 3D genome rewiring during mouse neural development. Cell 171, 557–572 e524 (2017). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Within the 5C regions, activity-induced loops are rare and connect to genes with large activity-dependent increases in expression, whereas pre-existing loops are more abundant but correlate with only minor gene expression changes.

    “These results suggest that, within our 5C regions, activity-induced loops are rare and connect to genes with large activity-dependent increases in expression, whereas pre-existing loops are more abundant but correlate with only minor gene expression changes.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: H3K27ac signal correlates with enhancer and promoter activity.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Loop dysfunction could be possible owing to common SNVs in sporadic ASD and schizophrenia.

    “thus loop dysfunction could be possible owing to common SNVs in sporadic ASD and schizophrenia.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    In the ABC model, the multiplication of enhancer activity and 3D interaction frequency was the best predictor of enhancer-target gene pairs.

    “In the ABC model, the multiplication of enhancer activity and 3D interaction frequency was the best predictor of enhancer–target gene pairs37.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Fulco, C. P. et al. Activity-by-contact model of enhancer-promoter regulation from thousands of CRISPR perturbations. Nat. Genet. 51, 1664–1669 (2019). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Genome misfolding has been reported in fragile X syndrome, the leading monogenic cause of ASD, as well as other human diseases.

    “Genome misfolding has been reported in fragile X syndrome48, the leading monogenic cause of ASD, as well as other human diseases49”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [48] Sun, J. H. et al. Disease-associated short tandem repeats co-localize with chromatin domain boundaries. Cell 175, 224–238.e15 (2018). source

      Not checked in the free run.

    • cites [49] Norton, H. K. & Phillips-Cremins, J. E. Crossed wires: 3D genome misfolding in human disease. J. Cell Biol. 216, 3441–3452 (2017). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    H3K27ac enrichment was confirmed before sequencing by qPCR enrichment of primer pairs designed to the Arc, synaptotagmin 1, and Tcf25 promoter regions.

    “H3K27ac enrichment was confirmed before sequencing by querying the immunoprecipitation or input quantitative PCR (qPCR) enrichment of primer pairs designed to the Arc, synaptotagmin 1, and Tcf25 promoter regions.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The Arc interaction falls below the 30-kb distance threshold and is not formally added to the class 1 loop list.

    “We note that the Arc interaction falls below our 30-kb distance threshold and therefore is not formally added to the class 1 loop list”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    More than 90% of disease-associated single-nucleotide variants are localized in noncoding regions with unknown target genes.

    “More than 90% of disease-associated SNVs (daSNVs) are localized in noncoding regions with unknown target genes40”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Maurano, M. T. et al. Systematic localization of common disease-associated variation in regulatory DNA. Science 337, 1190–1195 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Loops that are induced by neural stimulation are relatively rare but exhibit a markedly higher effect on activity-dependent upregulation of distal target genes.

    “Moreover, our 5C results suggest that loops that are induced by neural stimulation are relatively rare but exhibit a markedly higher effect on activity-dependent upregulation of distal target genes.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: H3K27ac signal correlates with enhancer and promoter activity.

  • May combine two claims.

    Interpretationown data

    Secondary response genes engage in a complex network of long-range loops, whereas immediate early genes form simple, short-range loops to activity-induced enhancers to facilitate rapid activation independent of new protein synthesis.

    “Together, these data are consistent with our working model in which SRGs engage in a complex network of long-range loops, whereas IEGs form simple, short-range loops to activity-induced enhancers to facilitate rapid activation independent of new protein synthesis”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationown data

    Rapid activity-induced enhancer switching via alternative looping might be a mechanistic aspect of IEG upregulation.

    “suggesting that rapid activity-induced enhancer switching via alternative looping might be a mechanistic aspect of IEG upregulation”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Bdnf loop and enhancer dynamics are significantly delayed compared to those of Fos and Arc, corroborating the model that slower interaction kinetics may contribute to secondary response gene delayed expression.

    “Thus, Bdnf loop and enhancer dynamics are significantly delayed in comparison to those of Fos and Arc, corroborating our model that slower interaction kinetics may contribute to SRGs delayed expression.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The SRG Nr4a3 engages in multiple long-range contacts over several hundred kb after neuronal stimulation.

    “Consistent with our observations, another study reported—using H3K4me3 proximity ligation assisted ChIP–seq (PLAC-seq)—that the SRG Nr4a3 engages in multiple long-range contacts over several hundred kb after neuronal stimulation26.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Yamada, T. et al. Sensory experience remodels genome architecture in neural circuit to drive motor learning. Nature 569, 708–713 (2019). source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    Results were consistent across 2 culture batches, 4 total 5C replicates, 3 RNA-seq replicates, and H3K27ac ChIP replicate analyzed.

    “Results were consistent across 2 culture batches, 4 total 5C replicates, 3 RNA-seq replicates, and H3K27ac ChIP replicate analyzed.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Treatment conditions were evenly distributed across culture batches and treatments were randomly assigned to culture dishes within each batch.

    “Treatment conditions were evenly distributed across culture batches and treatments were randomly assigned to culture dishes within each batch.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    No statistical methods were used to pre-determine sample sizes, but the sample sizes are similar to those reported in previous publications.

    “No statistical methods were used to pre-determine sample sizes but our sample sizes are similar to those reported in previous publications17,27,28.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [17] Rao, S. S. et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665–1680 (2014). source

      Not checked in the free run.

    • cites [27] Beagan, J. A. et al. YY1 and CTCF orchestrate a 3D chromatin looping switch during early neural lineage commitment. Genome Res 27, 1139–1152 (2017). source

      Not checked in the free run.

    • cites [28] Beagan, J. A. et al. Local genome topology can exhibit an incompletely rewired 3D-folding state during somatic cell reprogramming. Cell Stem. Cell 18, 611–624 (2016). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Resulting P values were corrected for multiple testing using the Benjamini-Hochberg procedure.

    “Resulting P values were corrected for multiple testing using the Benjamini–Hochberg procedure.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Data collection and analysis were not performed blind to the conditions of the experiments.

    “Data collection and analysis were not performed blind to the conditions of the experiments.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Residuals were plotted to confirm approximate normal distributions.

    “Residuals were plotted to confirm approximate normal distributions.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Genes were not considered if they fell within 200 kb of the edges of our 5C regions because we could not accurately capture their looping profiles.

    “In addition, genes were not considered if they fell within 200 kb of the edges of our 5C regions because we could not accurately capture their looping profiles.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    No animals or data points were excluded from the analyses.

    “No animals or data points were excluded from the analyses.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Three replicates spanning two culture batches were prepared, pooled, and sequenced to depths of greater than 60 million reads per library to minimize and identify technical variation.

    “To minimize and identify technical variation, three replicates spanning two culture batches were prepared, pooled, and sequenced to depths of greater than 60 million reads per library.”
    Quote in the paperNot a substantial claim
38 of 38

  • The paper relies on this without support.

    H3K27ac signal correlates with enhancer and promoter activity.

    “As the histone mark H3 lysine 27 acetylation (H3K27ac) correlates with enhancer and promoter activity”

  • The paper relies on this without support.

    Activity-dependent enhancer classes identified in mouse cortical neurons correspond to functionally equivalent regulatory elements in human brain.

    “We lifted-over our activity-dependent enhancer classes to the human genome and classified 4,098 class 2 and 3,822 class 3 loops from human brain tissue”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Rapid IEGs are assigned two different source-category names

    Minor

    The methods identify the rapid IEG category in reference 9 as "rIEGs," while the Extended Data caption identifies it as "rPRGs."

1 of 1

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Authors
Beagan, J. A., Pastuzyn, E. D., Fernandez, L. R., Guo, M. H., Feng, K., Titus, K. R., Chandrashekar, H., Shepherd, J. D., & Phillips-Cremins, J. E.
Affiliations
  • University of Pennsylvania (US)
  • University of Utah (US)
  • Hospital of the University of Pennsylvania (US)
Corresponding author
Shepherd, Jason D.
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2020-05-25
Volume
23
Issue
6
Pages
707-717
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/s41593-020-0634-6
PMC
PMC7558717
OpenAlex
W3027029189
Cited by
143
References
69
Citations by year
2026: 13 · 2025: 20 · 2024: 23 · 2023: 29 · 2022: 28 · 2021: 23 · 2020: 7
FWCI
7.06
Type
journal article
Language
en
Update notices
correction (2020-07-23)
Open access
Licence
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (U01HL129998)
  • National Institute of Mental Health (DP2MH110247, R01MH112766)
  • National Institute of Neurological Disorders and Stroke (R01NS114226)
  • National Institute of Biomedical Imaging and Bioengineering (T32EB009384)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
3D genome organization, activity-dependent gene expression, immediate early genes, FOS, Arc, brain-derived neurotrophic factor, chromatin remodeling, transcriptional kinetics, single nucleotide variants, autism spectrum disorder, schizophrenia, cortical neurons
MeSH terms
Animals, Bicuculline, Cytoskeletal Proteins, Humans, Nerve Tissue Proteins, Neurons, Tetrodotoxin, Time Factors, Gene Expression, Genome, Proto-Oncogene Proteins c-fos, Brain-Derived Neurotrophic Factor, Chromatin Assembly and Disassembly, Mice

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