Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA244660 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1238670.fastq.gz | Fastqsanger.gz | |||
| SRR1238671.fastq.gz | Fastqsanger.gz | |||
| SRR1238672.fastq.gz | Fastqsanger.gz | |||
| SRR1238673.fastq.gz | Fastqsanger.gz | |||
| SRR1238674.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
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Project description:Loss of neuronal 3D chromatin organization causes transcriptional and behavioral deficits related to serotonergic dysfunction [expression]
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Project description:The interior of the neuronal cell nucleus is a highly organized 3-dimensional (3D) structure in which regions of the genome that are millions of bases apart participate in specialized sub-structures with dedicated functions. To investigate neuronal chromatin organization and dynamics in vivo, we generated bitransgenic mice that express histone GFP-tagged H2B in principal neurons of the forebrain. Surprisingly, the expression of this chimeric histone in mature neurons causes chromocenter declustering and disrupts the association of heterochromatin with the nuclear lamina. The loss of these structures does not affect neuronal viability but is associated with specific transcriptional and behavioral deficits related to serotonergic dysfunction. Overall, our results demonstrate that the 3D-organization of chromatin in the neuronal nucleus supports an additional level of epigenetic regulation of gene expression that critically influences neuronal function and indicate that some loci associated with neuropsychiatric disorders may be particularly sensitive to changes in chromatin architecture.
2014-07-18 | GSE56809 | GEO
Project description:The interior of the neuronal cell nucleus is a highly organized 3-dimensional (3D) structure in which regions of the genome that are millions of bases apart participate in specialized sub-structures with dedicated functions. To investigate neuronal chromatin organization and dynamics in vivo, we generated bitransgenic mice that express histone GFP-tagged H2B in principal neurons of the forebrain. Surprisingly, the expression of this chimeric histone in mature neurons causes chromocenter declustering and disrupts the association of heterochromatin with the nuclear lamina. The loss of these structures does not affect neuronal viability but is associated with specific transcriptional and behavioral deficits related to serotonergic dysfunction. Overall, our results demonstrate that the 3D-organization of chromatin in the neuronal nucleus supports an additional level of epigenetic regulation of gene expression that critically influences neuronal function and indicate that some loci associated with neuropsychiatric disorders may be particularly sensitive to changes in chromatin architecture. Genome-wide profiling by high throughput sequencing of H3K27me3 in the adult hippocampus of CaMKII-tTA/tetO-H2BGFP (H2BGFP) and their wild-type littermates mice (WT). Chromatin immunoprecipitation (ChIP) was carried out using pooled hippocampal tissue from 3 mice (one hippocampus per mouse). One DNA library was constructed per genotype. Each DNA library was prepared from pooled immunoprecipitated DNA from 4 independent ChIP assays. In total, tissue from 12 different mice was used to prepare each DNA library. 60% of a lane was used to perform single end (1x50bp) multiplex sequencing in HiSeq 2500 apparatus (Illumina). Each library, was sequenced in duplicate (in two independent sequencing runs. Technical replicates).
2014-07-18 | E-GEOD-56809 | biostudies-arrayexpress
Project description:The interior of the eukaryotic cell nucleus is a highly organized 3D structure. In mature hippocampal and cortical pyramidal neurons, transcriptionally silent DNA is typically compacted in a few clusters referred to as chromocenters that are strongly stained with DNA intercalating agents like DAPI and whose function is still uncertain. We found that this 3D structure was severely disrupted by the incorporation of the chimeric histone H2BGFP into neuronal chromatin. Experiments in inducible and forebrain restricted bitransgenic mice demonstrated that the expression of this histone alters the higher-order organization of neuronal heterochromatin and causes a complex behavioral phenotype that includes hyperactivity, and social interaction, prepulse inhibition and cognitive defects. This phenotype was associated with highly specific transcriptional deficits that affected several serotonin receptor genes located at the edge of gene desert regions. Pharmacological and electrophysiological experiments indicate that this epigenetically-induced hyposerotonergic state may underlie the behavioral defects. Our results suggest a new role for perinuclear heterochromatin and chromocenter organization in the epigenetic regulation of neuronal gene expression and mental illness. We used microarrays to detect differential gene expression in transgenic mice expressing histone H2BGFP in the forebrain. We obtained triplicate samples (biological replicates) of either genotype (wild-type and H2BGFP mice). Each sample contained pooled total RNA from the hippocampi of 2 three-month old genotype-matched mice.
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Project description:Impairment of methylglyoxal detoxification systems causes mitochondrial dysfunction and behavioral deficits
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2022-08-23 | PXD029230 | Pride
Project description:Early-life stress has been linked to multiple neurodevelopmental and neuropsychiatric deficits. Our previous studies have linked maternal presence/absence from the nest in developing rat pups to changes in prefrontal cortex activity. Furthermore, we have shown that these changes are modulated by serotonergic signaling. Here we test whether changes in prefrontal cortex activity during early-life affect the developing cortex leading to behavioral alterations in the adult. We show that inhibiting the prefrontal cortex of mouse pups leads to cognitive deficits in the adult comparable to those seen following maternal separation. Moreover, we show that activating the prefrontal cortex during maternal separation can prevent these behavioral deficits. To test how maternal separation affects the transcriptional profile of the prefrontal cortex we performed single-nucleus RNA sequencing. Maternal separation lead to differential gene expression almost exclusively in inhibitory neurons. Among others, we found changes in GABAergic and serotonergic pathways in these interneurons. Interestingly, both maternal separation and early-life prefrontal cortex inhibition led to changes in physiological responses in prefrontal activity to GABAergic and serotonergic antagonists that were similar to the responses of more immature brains. Prefrontal activation during maternal separation prevented these changes. These data point to a crucial role of prefrontal cortex activity during early-life in behavioral expression in adulthood
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Project description:The dorsal raphe nucleus (DRN) is an important source of neuromodulators and has been implicated in a wide variety of behavioral and neurological disorders. The DRN is subdivided into distinct anatomical subregions comprised of multiple cell types, and its complex cellular organization has impeded efforts to investigate the distinct circuit and behavioral functions of its subdomains. Here we used single-cell RNA sequencing, in situ hybridization, anatomical tracing, and spatial correlation analysis to map the transcriptional and spatial profiles of cells from the mouse DRN. Our analysis of 39,411 single-cell transcriptomes revealed at least 18 distinct neuron subtypes and 5 serotonergic neuron subtypes with distinct molecular and anatomical properties, including a serotonergic neuron subtype that preferentially innervates the basal ganglia. Our study lays out the molecular organization of distinct serotonergic and non-serotonergic subsystems, and will facilitate the design of strategies for further dissection the DRN and its diverse functions.
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