Ontology highlight
ABSTRACT:
PROVIDER: PRJNA145083 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR342251.fastq.gz | Fastqsanger.gz | |||
| SRR342252.fastq.gz | Fastqsanger.gz | |||
| SRR342253.fastq.gz | Fastqsanger.gz | |||
| SRR342254.fastq.gz | Fastqsanger.gz | |||
| SRR342255.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function [ChIP-Seq]
| PRJNA155291 | ENA
Project description:Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function [visual cortex]
| PRJNA155261 | ENA
Project description:Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function [cultured cortical neurons]
| PRJNA155259 | ENA
Project description:Autism spectrum disorders such as Rett syndrome (RTT) have been hypothesized to arise from defects in experience-dependent synapse maturation. RTT is caused by mutations in MECP2, a nuclear protein that becomes phosphorylated at S421 in response to neuronal activation. We show here that disruption of MeCP2 S421 phosphorylation in vivo results in defects in synapse development and behavior, implicating activity-dependent regulation of MeCP2 in brain development and RTT. We investigated the mechanism by which S421 phosphorylation regulates MeCP2 function and show by chromatin immunoprecipitation-sequencing that this modification occurs on MeCP2 bound across the genome. The phosphorylation of MeCP2 S421 appears not to regulate the expression of specific genes; rather, MeCP2 functions as a histone-like factor whose phosphorylation may facilitate a genome-wide response of chromatin to neuronal activity during nervous system development. We propose that RTT results in part from a loss of this experience-dependent chromatin remodeling. Gene expression analysis of RNA isolated from P17 mouse visual cortex was performed comparing global gene expression between Wild-Type and MeCP2 S421A knock-in mice. We isolated RNA from the visual cortex of 4 wild-type and 4 MeCP2 S421A littermate P17 Mice, and analyzed mRNA expression using the Affymetrix Mouse Gene 1.0 ST microarray platform.
2011-09-07 | E-GEOD-31850 | biostudies-arrayexpress
Project description:Autism spectrum disorders such as Rett syndrome (RTT) have been hypothesized to arise from defects in experience-dependent synapse maturation. RTT is caused by mutations in MECP2, a nuclear protein that becomes phosphorylated at S421 in response to neuronal activation. We show here that disruption of MeCP2 S421 phosphorylation in vivo results in defects in synapse development and behavior, implicating activity-dependent regulation of MeCP2 in brain development and RTT. We investigated the mechanism by which S421 phosphorylation regulates MeCP2 function and show by chromatin immunoprecipitation-sequencing that this modification occurs on MeCP2 bound across the genome. The phosphorylation of MeCP2 S421 appears not to regulate the expression of specific genes; rather, MeCP2 functions as a histone-like factor whose phosphorylation may facilitateM-CM-^BM-BM- a genome-wide response of chromatin to neuronal activity during nervous system development. We propose that RTT results in part from a loss of this experience-dependent chromatin remodeling. To examine MeCP2 binding across the neuronal genome and where on the genome MeCP2 is phosphorylated at Serine 421 in response to neuronal activity we performed anti-total MeCP2 and anti-phospho-Serine 421 specific Chromatin immunoprecipitation from cultured cortical neurons that were either left unstimulated or membrane depolarized for 2 hours by addition of 55mM KCl to the media. ChIP DNA was verified for successful IP by qPCR then cloned and sequenced using ABI SOLiD system 4. ChIP was performed from E16 +7DIV disociated cortical cultures from one or two independent dissections using an anti-c-terminal antiserum recognizing MeCP2 independent of its phosphorylation state or with an anti-pS421 antiserum that specifically immunoprecipitates MeCP2 phosphorylated at serine 421. Samples were qPCR validated and sequenced using ABI SOLiD system 4 library preparation and sequencing.
2011-09-08 | E-GEOD-31951 | biostudies-arrayexpress
Project description:Autism spectrum disorders such as Rett syndrome (RTT) have been hypothesized to arise from defects in experience-dependent synapse maturation. RTT is caused by mutations in MECP2, a nuclear protein that becomes phosphorylated at S421 in response to neuronal activation. We show here that disruption of MeCP2 S421 phosphorylation in vivo results in defects in synapse development and behavior, implicating activity-dependent regulation of MeCP2 in brain development and RTT. We investigated the mechanism by which S421 phosphorylation regulates MeCP2 function and show by chromatin immunoprecipitation-sequencing that this modification occurs on MeCP2 bound across the genome. The phosphorylation of MeCP2 S421 appears not to regulate the expression of specific genes; rather, MeCP2 functions as a histone-like factor whose phosphorylation may facilitate a genome-wide response of chromatin to neuronal activity during nervous system development. We propose that RTT results in part from a loss of this experience-dependent chromatin remodeling. Gene expression analysis of RNA isolated from P17 mouse visual cortex was performed comparing global gene expression between Wild-Type and MeCP2 S421A knock-in mice.
2011-09-08 | GSE31850 | GEO
Project description:Autism spectrum disorders such as Rett syndrome (RTT) have been hypothesized to arise from defects in experience-dependent synapse maturation. RTT is caused by mutations in MECP2, a nuclear protein that becomes phosphorylated at S421 in response to neuronal activation. We show here that disruption of MeCP2 S421 phosphorylation in vivo results in defects in synapse development and behavior, implicating activity-dependent regulation of MeCP2 in brain development and RTT. We investigated the mechanism by which S421 phosphorylation regulates MeCP2 function and show by chromatin immunoprecipitation-sequencing that this modification occurs on MeCP2 bound across the genome. The phosphorylation of MeCP2 S421 appears not to regulate the expression of specific genes; rather, MeCP2 functions as a histone-like factor whose phosphorylation may facilitate a genome-wide response of chromatin to neuronal activity during nervous system development. We propose that RTT results in part from a loss of this experience-dependent chromatin remodeling. To examine MeCP2 binding across the neuronal genome and where on the genome MeCP2 is phosphorylated at Serine 421 in response to neuronal activity we performed anti-total MeCP2 and anti-phospho-Serine 421 specific Chromatin immunoprecipitation from cultured cortical neurons that were either left unstimulated or membrane depolarized for 2 hours by addition of 55mM KCl to the media. ChIP DNA was verified for successful IP by qPCR then cloned and sequenced using ABI SOLiD system 4.
2011-09-08 | GSE31951 | GEO
Project description:Mutations of MECP2 (Methyl-CpG Binding Protein 2) cause Rett Syndrome. As a chromatin associated multifunctional protein, how MeCP2 integrates external signals and regulates neuronal function remain unclear. While neuronal activity-induced phosphorylation of MeCP2 at serine 421 (S421) has been reported, the full spectrum of MeCP2 phosphorylation together with the in vivo function of such modifications are yet to be revealed. Here we report the identification of several novel MeCP2 phosphorylation sites in normal and epileptic brains from multiple species. We demonstrate that serine 80 (S80) phosphorylation of MeCP2 is critical as its mutation into alanine (S80A) in transgenic knock-in mice leads to locomotor deficits. S80A mutation attenuates MeCP2 chromatin association at several gene promoters in resting neurons and leads to transcription changes of a small number of genes. Calcium influx in neurons causes dephosphorylation at S80, potentially contributing to its dissociation from the chromatin. We postulate that phosphorylation of MeCP2 modulates its dynamic function in neurons transiting between resting and active states within neural circuits that underlie behaviors. E 15.5 Mecp2 -/y cortical neurons were infected with lentivirus expressing wild-type and S80A mutant MeCP2 at similar protein expression level. 2 biological independent samples and dye swap were used for this set (GSM367413) and replicate 2 set (GSM367414).
2009-02-10 | E-GEOD-14715 | biostudies-arrayexpress
Project description:Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement
| PRJNA1026629 | ENA
Project description:Experience-dependent gene transcription is required for nervous system development and function. However, the DNA regulatory elements that control this program of gene expression are not well defined. Here we characterize the enhancers that function across the genome to mediate activity-dependent transcription in neurons. While ~12,000 putative activity-regulated enhancer sequences have previously been identified that are enriched for H3K4me1 and the histone acetyltransferase CBP, we find that this chromatin signature is not sufficient to distinguish which of these regulatory sequences are actively engaged in promoting activity-dependent transcription. We show here that a subset of H3K4me1/CBP positive enhancers that is enriched for H3K27 acetylation (H3K27ac) in vivo, and shows increased H3K27ac upon membrane depolarization of cortical neurons, function to regulate activity-dependent transcription. The function of many of these activity-regulated enhancers appears to be dependent on the binding of FOS, a protein that had previously been thought to interact primarily with the promoters of activity-regulated genes. Furthermore, many of these target genes in cortical neurons encode neuron specific proteins that regulate synaptic development and function. These findings suggest that FOS functions at enhancers to control activity-dependent gene programs that are critical for nervous system function, and provide a resource of activity-dependent enhancers that may give insight into genetic variation that contributes to brain development and disease. Genome-wide maps of H3K27ac and AP1 transcription factors (CFOS, FOSB, JUNB) before and after neuronal activity in mouse cortical neurons.
2014-09-07 | E-GEOD-60192 | biostudies-arrayexpress