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Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE152956 | GEO | 2020/06/23

REPOSITORIES: GEO

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Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble.

Project description:The epigenome and three-dimensional (3D) genomic architecture are emerging as key factors in the dynamic regulation of different transcriptional programs required for neuronal functions. In this study, we used an activity-dependent tagging system in mice to determine the epigenetic state, 3D genome architecture and transcriptional landscape of engram cells over the lifespan of memory formation and recall. Our findings reveal that memory encoding leads to an epigenetic priming event, marked by increased accessibility of enhancers without the corresponding transcriptional changes. Memory consolidation subsequently results in spatial reorganization of large chromatin segments and promoter-enhancer interactions. Finally, with reactivation, engram neurons use a subset of de novo long-range interactions, where primed enhancers are brought in contact with their respective promoters to upregulate genes involved in local protein translation in synaptic compartments. Collectively, our work elucidates the comprehensive transcriptional and epigenomic landscape across the lifespan of memory formation and recall in the hippocampal engram ensemble.

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Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble

2020-06-23 | GSE152954 | GEO

Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble

Project description:Purpose: we utilized a mouse model that permanently labels neurons activated throughout a specific experience to decipher the interplay between chromatin accessibility, 3D-chromatin architecture and transcriptional changes across different memory phases. Non activated (basal) and activated neurons during memory encoding (early), consolidation (late) and recall (reactivated) were sorted and subjected to nuclear RNA sequencing (nRNA-seq) to determine gene expression, ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) to assess chromatin accessibility, chromosome conformation capture (Hi-C) to identify global 3D -genome architecture and promoter capture Hi-C to identify the long range promoter-enhancer interactions. Results: We have found that during each memory phase, the same promoters interact more frequently with a distinct subset of enhancers (i.e. unique). We also identified a smaller subset of interactions in which the promoters were interacting with the same enhancers across different memory phases (i.e. common). Furthermore, Reactivated neurons presented significantly stronger interaction scores (as calculated by CHiCAGO). Hence, although the number of unique interactions was similar across early, late and reactivated states, stronger interaction scores indicate that specific promoter- enhancer interactions occur more frequently during memory recall.

2020-06-23 | GSE152955 | GEO

Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble

Project description:Purpose: we utilized a mouse model that permanently labels neurons activated throughout a specific experience to decipher the interplay between chromatin accessibility, 3D-chromatin architecture and transcriptional changes across different memory phases. Non activated (basal) and activated neurons during memory encoding (early), consolidation (late) and recall (reactivated) were sorted and subjected to nuclear RNA sequencing (nRNA-seq) to determine gene expression, ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) to assess chromatin accessibility, chromosome conformation capture (Hi-C) to identify global 3D -genome architecture and promoter capture Hi-C to identify the long range promoter-enhancer interactions. Results: Our analysis revealed dynamic changes in compartments organization, where we observed re-localization of large chromatin segments from inactive to permissive environment (and vice versa) during the initial and late phase of memory formation. Interestingly, 52% of the regions in the early phase that switched from B to A maintained that state in the late phase (i.e. remained in state A. Moreover, nearly all these regions significantly overlapped with gained DARs identified in our ATAC-seq analysis, confirming the transition of sub-compartment from inactive to permissive environment. This data indicates that while some loci undergo sub-compartment switching across different memory phases, the majority are stable, correlate with chromatin accessibility and therefore might contribute to long-term changes in neuronal properties and function after initial activation.

2020-06-23 | GSE152953 | GEO

Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble

Project description:Purpose: we utilized a mouse model that permanently labels neurons activated throughout a specific experience to decipher the interplay between chromatin accessibility, 3D-chromatin architecture and transcriptional changes across different memory phases. Non activated (basal) and activated neurons during memory encoding (early), consolidation (late) and recall (reactivated) were sorted and subjected to nuclear RNA sequencing (nRNA-seq) to determine gene expression, ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) to assess chromatin accessibility, chromosome conformation capture (Hi-C) to identify global 3D -genome architecture and promoter capture Hi-C to identify the long range promoter-enhancer interactions. Results: Our differentially expressed gene (DEG) analysis revealed relatively low amount of changes in the early phase, when compared to basal-state neurons (Basal vs. Early). In contrast, neurons from late phase presented higher numbers of DEGs despite there being more similarity in chromatin accessibility at these time points (Early vs. Late; Late vs. Reactivated). Our studies illuminate for the first time the unique transcriptional landscape of reactivated engram cells where we observed up-regulation of genes involved in mRNA transport and local protein translation in synaptic compartments. These changes corresponded to morphological and functional changes in those neurons.

2020-06-23 | GSE152775 | GEO

Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble

Project description:Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble

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Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble

Project description:Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble

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Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble

Project description:Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble

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Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble

Project description:Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble