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GSE50822
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The subunits of voltage-gated calcium channels regulate surface expression and gating of CaV1 and CaV2 1 subunits, and thus contribute to neuronal excitability, neurotransmitter release and calcium-induced gene regulation. In addition certain subunits are targeted into the nucleus, where they directly interact with the epigenetic machinery. Whereas their involvement in this multitude of functions is reflected by a great molecular heterogeneity of isoforms derived from four genes and abundant alternative splicing, little is known about the roles of individual variants in specific neuronal functions. In the present study, an alternatively spliced 4 subunit lacking the variable N-terminus (4e) is identified. It is highly expressed in mouse cerebellum and cultured cerebellar granule cells (CGC) and modulates P/Q-type calcium currents in tsA cells and CaV2.1 surface expression in neurons. Compared to the other two known full-length 4 variants (4a, 4b) 4e is most abundantly expressed in the distal axon, but lacks nuclear targeting properties. To examine the importance of nuclear targeting of 4 subunits for transcriptional regulation, we performed whole genome expression profiling of CGCs from lethargic mice individually reconstituted with 4a, 4b, and 4e. Notably, the number of genes regulated by each 4 splice variant correlated with the rank order of their nuclear targeting properties (4b> 4a> 4e). Together these findings support isoform-specific functions of 4 splice variant in neurons, with 4b playing a dual role in channel modulation and gene regulation, while the newly detected 4e variant serves exclusively in calcium channel-dependent functions.
Publication Title
Differential neuronal targeting of a new and two known calcium channel β4 subunit splice variants correlates with their regulation of gene expression.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Rapid responses to biotic and abiotic insults are crucial for plant survival. We examined the very early (10 min) wound transcriptome in order to increase our understanding regarding this critical intial phase of the plant response to stress. Our analysis revealed a rapid induction of stress-related transcripts that was distinct from the long term events which are dominated by jasmonic pathway responses.
Publication Title
Singlet oxygen signatures are detected independent of light or chloroplasts in response to multiple stresses.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genomic responses from the estrogen-responsive element-dependent signaling pathway mediated by estrogen receptor alpha are required to elicit cellular alterations.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In addition to the estrogen responsive element (ERE)-dependent gene expression, E2-ERbeta regulates transcription through functional interactions with transfactors bound to their cognate regulatory elements on DNA, hence the ERE-independent signaling pathway. However, the relative importance of the ERE-independent pathway in E2-ERbeta signaling is unclear. Our studies in infected ER-negative cell models with an ERbeta mutant (ERbetaDBD) that functions exclusively at the ERE-independent pathway demonstrated that genomic responses assessed by microarrays from the ERE-independent pathway to E2-ERbeta are not sufficient to alter cellular growth, death or motility. These findings suggest that the ERE-dependent pathway is the canonical E2-ERbeta signaling in model cell lines.
Publication Title
Genomic responses from the estrogen-responsive element-dependent signaling pathway mediated by estrogen receptor alpha are required to elicit cellular alterations.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In addition to the estrogen responsive element (ERE)-dependent gene expression, E2-ERalpha regulates transcription through functional interactions with transfactors bound to their cognate regulatory elements on DNA, hence the ERE-independent signaling pathway. However, the relative importance of the ERE-independent pathway in E2-ERalpha signaling is unclear. Our studies in infected ER-negative cell models with an ERalpha mutant (ERalpha 203/204/211E) that functions exclusively at the ERE-independent pathway demonstrated that genomic responses assessed by microarrays from the ERE-independent pathway to E2-ERalpha are not sufficient to alter cellular growth, death or motility. These findings suggest that the ERE-dependent pathway is the canonical E2-ERalpha signaling in model cell lines.
Publication Title
Genomic responses from the estrogen-responsive element-dependent signaling pathway mediated by estrogen receptor alpha are required to elicit cellular alterations.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In addition to the estrogen responsive element (ERE)-dependent gene expression, E2-ERalpha regulates transcription through functional interactions with transfactors bound to their cognate regulatory elements on DNA, hence the ERE-independent signaling pathway. However, the relative importance of the ERE-independent pathway in E2-ERalpha signaling is unclear. Our studies in infected ER-negative cell models with an ERalpha demonstrated that genomic responses assessed by microarrays from the alter cellular growth, death or motility.
Publication Title
Genomic responses from the estrogen-responsive element-dependent signaling pathway mediated by estrogen receptor alpha are required to elicit cellular alterations.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Samples of adherent and suspension cells undergoing reprogramming were collected at day 0, day2, day6, day15 (with doxycycline) and day25 (without doxycycline).
Publication Title
Derivation, expansion and differentiation of induced pluripotent stem cells in continuous suspension cultures.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 140 Downloadable Samples
NextSeq 550
Description
DNA is strictly compartmentalised within the nucleus to prevent autoimmunity despite this cGAS, a cytosolic sensor of dsDNA, is activated in autoinflammatory disorders and by DNA damage. Precisely how cellular DNA gains access to the cytoplasm remains to be determined. Here, we report that cGAS localises to micronuclei arising from genome instability in a model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells. These micronuclei occur after mis-segregation of DNA during cell division and consist of chromatin surrounded by their own nuclear membrane. Breakdown of the micronuclear envelope, a process associated with chromothripsis, leads to rapid accumulation of cGAS, providing a mechanism by which self-DNA becomes exposed to the cytosol. cGAS binds to and is activated by chromatin and consistent with a mitotic origin, micronuclei formation and the proinflammatory response following DNA-damage are cell-cycle dependent. Furthermore, by combining live-cell laser microdissection with single cell transcriptomics, we establish that induction of interferon stimulated gene expression occurs in micronucleated cells. We therefore conclude that micronuclei represent an important source of immunostimulatory DNA. As micronuclei formed from lagging chromosomes also activate this pathway, cGAS recognition of micronuclei may act as a cell-intrinsic immune surveillance mechanism detecting a range of neoplasia-inducing processes. Overall design: RNA-seq of 35 individual mouse embryonic fibroblasts 48 h after 1 Gy irradiation: 21 test (with micronuclei) and 14 controls (without micronuclei).
Publication Title
cGAS surveillance of micronuclei links genome instability to innate immunity.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples