Conditional knockout of p300 and Cbp in mouse rod photoreceptors
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE47699 | GEO | 2013/07/29
SECONDARY ACCESSION(S): PRJNA207336
REPOSITORIES: GEO
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Project description:Gene regulatory networks (GRNs) guiding differentiation of cell types and cell assemblies in the nervous system are poorly understood because of inherent complexities and interdependence of signaling pathways. Here, we report transcriptome dynamics of differentiating rod photoreceptors in the mammalian retina. Given that the transcription factor NRL determines rod cell fate, we performed expression profiling of developing NRL-positive (rods) and NRL-negative (S-cone-like) mouse photoreceptors. We identified a large-scale, sharp transition in the transcriptome landscape between postnatal days 6 and 10 concordant with rod morphogenesis. Rod-specific temporal DNA methylation corroborated gene expression patterns. De novo assembly and alternative splicing analyses revealed previously unannotated rod-enriched transcripts and the role of NRL in transcript maturation. Furthermore, we defined the relationship of NRL with other transcriptional regulators and downstream cognate effectors. Our studies provide the framework for comprehensive system-level analysis of the GRN underlying the development of a single sensory neuron, the rod photoreceptor.
2016-11-04 | GSE74657 | GEO
Project description:To better understand the mechanistic basis of aging and its relationship with retinal degeneration, we examined gene expression changes in aging rod photoreceptors. Rod photoreceptor cell death is a feature of normal retinal aging and is accelerated in many retinal degenerative diseases, including AMD, the leading cause of untreatable adult blindness in the United States and other western countries. To our knowledge, the examination of age-related gene expression changes in a specific neuronal cell-type is novel, and it has allowed us to identify significant age-related changes with better resolution than is possible with whole retina samples. We used flow cytometry and a transgenic mouse with GFP-tagged rod photoreceptors to purify this specific cell population, and gene expression changes were evaluated at three time points using microarrays and quantitative RT-PCR. Our results suggest that aging is progressive, beginning even in young adult mice. Although rod photoreceptors are highly specialized neurons, our analyses revealed changes in consensus pathways of aging, including oxidative phosphorylation and stress responses affecting transcription and inflammation. In addition, we identified stress response processes that may be especially relevant for the aging retina and retinal diseases, such as angiogenesis and nuclear receptor signaling pathways that affect retinoid and lipid metabolism. We used flow cytometry and a transgenic mouse with GFP-tagged rod photoreceptors to purify this specific cell population, and gene expression changes were evaluated at three time points using microarrays and quantitative RT-PCR.
2010-06-14 | E-GEOD-22317 | biostudies-arrayexpress
Project description:Purpose: The purpose of this study was to identify transcripts of rod photoreceptors of the zebrafish, an important animal model for vision science. Methods: Zebrafish rods, and non-rod retinal cells of the XOPS:eGFP transgenic line, were separated by cell dissociation and fluorescence-activated cell sorting (FACS), followed by RNA-seq. Validation studies used qPCR and in situ hybridization. Some transcripts were examined in sorted retinal cell populations of larval and juvenile retinas and regenerated adult retinas, and in a zebrafish model for rod degeneration. Results: At a false discovery rate of <0.01, 597 transcripts were upregulated in rods vs. non-rod retinal cells, and 1032 were downregulated. 13,324 total transcripts were detected in rods, including many not previously known to be expressed by rods. Transcripts enriched in rods from adult retinas were also enriched in rods from larval and juvenile retinas, and were also enriched in regenerated rods. Many transcripts enriched in rods were upregulated in retinas of wildtype retinas vs. those of a zebrafish model for rod degeneration. Conclusions: We report the generation of an RNA-seq dataset describing the rod transcriptome of the zebrafish, which is now available as a resource for further studies of rod photoreceptor biology and comparative transcriptomics.
2018-02-08 | GSE100062 | GEO
Project description:C4-2B prostate cancer cells were transfected with siRNA against a non-specific (NS) sequence, siRNA specifically targeting EP300, or siRNA specifically targeting CREBBP. We tested the hypothesis that their exists different subgroups of genes that are preferentially affected by p300 or CBP depletion. Cells were treated with 10nM dihydrotestosterone (DHT) for 16 hours and total RNA was extracted to check for changes in gene expression.
2011-12-15 | E-GEOD-31873 | biostudies-arrayexpress
Project description:Aging-associated functional decline and disease susceptibility are believed to be mediated, at least in part, through alterations in the epigenome. To explore epigenetic changes that might influence visual function with advanced age, we performed whole genome bisulfite sequencing of purified mouse rod photoreceptors at four different ages and identified 2054 genomic regions that gain or lose DNA methylation. Differentially methylated regions (DMRs) clustered at chromosomal hotspots, especially on Chromosome 10 that included a longevity interactome. DMRs were preferentially detected at an early stage of aging in long neuronal genes and in rod-specific regulatory regions containing open chromatin domains and H3K27 acetylation. Integration of methylome to age-related transcriptome changes, chromatin signatures and first order protein-protein interactions uncovered an enrichment of DMRs in pathways associated with aging, longevity, synaptic function, and energy homeostasis. In concordance, we detected reduced mitochondrial maximum reserve capacity with retinal age in ex vivo assays. Our study reveals age-dependent genomic and chromatin features susceptible to DNA methylation changes in rod photoreceptors and identifies associations with established and cell type-specific pathways altered in aging.
2020-03-10 | GSE134872 | GEO
Project description:To better understand the mechanistic basis of aging and its relationship with retinal degeneration, we examined gene expression changes in aging rod photoreceptors. Rod photoreceptor cell death is a feature of normal retinal aging and is accelerated in many retinal degenerative diseases, including AMD, the leading cause of untreatable adult blindness in the United States and other western countries. To our knowledge, the examination of age-related gene expression changes in a specific neuronal cell-type is novel, and it has allowed us to identify significant age-related changes with better resolution than is possible with whole retina samples. We used flow cytometry and a transgenic mouse with GFP-tagged rod photoreceptors to purify this specific cell population, and gene expression changes were evaluated at three time points using microarrays and quantitative RT-PCR. Our results suggest that aging is progressive, beginning even in young adult mice. Although rod photoreceptors are highly specialized neurons, our analyses revealed changes in consensus pathways of aging, including oxidative phosphorylation and stress responses affecting transcription and inflammation. In addition, we identified stress response processes that may be especially relevant for the aging retina and retinal diseases, such as angiogenesis and nuclear receptor signaling pathways that affect retinoid and lipid metabolism.
2010-06-15 | GSE22317 | GEO
Project description:Through ChIP-Seq analysis with the Illumina Whole Genome Analyzer, we identify binding sites for P300 (EP300) and CBP (CREBBP) in Human glioblastoma T98G cells that were cell cycle synchronized before and after stimulation. In our analysis, we focused on the identification of genes differentially bound by P300 and CBP. ChIP-seq with P300 and CBP antibodies over 2 timepoints
2010-03-30 | E-GEOD-21026 | biostudies-arrayexpress
Project description:Aging-associated functional decline and disease susceptibility are believed to be mediated, at least in part, through alterations in the epigenome. To explore epigenetic changes that might influence visual function with advanced age, we performed whole genome bisulfite sequencing of purified mouse rod photoreceptors at four different ages and identified 2054 genomic regions that gain or lose DNA methylation. Differentially methylated regions (DMRs) clustered at chromosomal hotspots, especially on Chromosome 10 that included a longevity interactome. DMRs were preferentially detected at an early stage of aging in long neuronal genes and in rod-specific regulatory regions containing open chromatin domains and H3K27 acetylation. Integration of methylome to age-related transcriptome changes, chromatin signatures and first order protein-protein interactions uncovered an enrichment of DMRs in pathways associated with aging, longevity, synaptic function, and energy homeostasis. In concordance, we detected reduced mitochondrial maximum reserve capacity with retinal age in ex vivo assays. Our study reveals age-dependent genomic and chromatin features susceptible to DNA methylation changes in rod photoreceptors and identifies associations with established and cell type-specific pathways altered in aging.
2020-03-10 | GSE137935 | GEO
Project description:Aging-associated functional decline and disease susceptibility are believed to be mediated, at least in part, through alterations in the epigenome. To explore epigenetic changes that might influence visual function with advanced age, we performed whole genome bisulfite sequencing of purified mouse rod photoreceptors at four different ages and identified 2054 genomic regions that gain or lose DNA methylation. Differentially methylated regions (DMRs) clustered at chromosomal hotspots, especially on Chromosome 10 that included a longevity interactome. DMRs were preferentially detected at an early stage of aging in long neuronal genes and in rod-specific regulatory regions containing open chromatin domains and H3K27 acetylation. Integration of methylome to age-related transcriptome changes, chromatin signatures and first order protein-protein interactions uncovered an enrichment of DMRs in pathways associated with aging, longevity, synaptic function, and energy homeostasis. In concordance, we detected reduced mitochondrial maximum reserve capacity with retinal age in ex vivo assays. Our study reveals age-dependent genomic and chromatin features susceptible to DNA methylation changes in rod photoreceptors and identifies associations with established and cell type-specific pathways altered in aging.
2020-03-10 | GSE134871 | GEO
Project description:Epigenetic and transcriptional changes in aging mouse rod photoreceptors
| PRJNA556663 | ENA