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SRP144212
Homo sapiens
56 Downloadable Samples
Illumina HiSeq 2500
Description
While activation of canonical NF-?B signaling through the IKK complex is well studied, few regulators of NIK-dependent non-canonical p52 nuclear translocation have been identified. We discovered a novel role for cyclin dependent kinase 12 (CDK12) in transcriptionally regulating the non-canonical NF-?B pathway. High-content phenotypic screening identified a novel compound, 919278, which inhibits lymphotoxin ß receptor (LTßR)- and FN14-dependent p52 nuclear translocation, but not TNFa receptor (TNFR)-mediated, canonical NF-?B p65 nuclear translocation. Chemoproteomics identified cyclin dependent kinase 12 (CDK12) as the target of 919278. CDK12 inhibition by 919278, THZ1, or siRNA knock down all affect similar global transcriptional changes and prevent LTßR and FN14-dependent MAP3K14 (NIK) mRNA induction and subsequent protein accumulation. In addition, 919278 and THZ1 treatment reduce RNA Pol II CTD phosphorylation. This powerful approach of coupling a phenotypic screen with chemoproteomics revealed a novel regulatory pathway of the non-canonical NF-?B pathway that could serve as a therapeutic target in autoimmunity and cancer. Overall design: There are TWEAK stimulated and unstimulated conditions, 4hr and 24hr time points. 7 treatments (DMSO, BIO0702697, BIO0919278, BIO032202, NTsiRNA, siRNAs523626, siRNAs523629) in duplicates. In total, 56 sample were sequenced and analyzed.
Publication Title
CDK12-mediated transcriptional regulation of noncanonical NF-κB components is essential for signaling.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
View Samples- Homo sapiens
- 59 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
We identified fibro-inflammatory and keratin gene expression signatures in systemic sclerosis skin.
Publication Title
Dissecting the heterogeneity of skin gene expression patterns in systemic sclerosis.
Sample Metadata Fields
Age, Specimen part, Race, Subject, Time
View Samples- Homo sapiens
- 59 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We identified eighty two skin transcripts significantly correlated with the severity of interstitial lung disease (ILD) in systemic sclerosis.
Publication Title
Skin gene expression correlates of severity of interstitial lung disease in systemic sclerosis.
Sample Metadata Fields
Age, Specimen part, Race, Subject
View Samples- Arabidopsis thaliana
- 31 Downloadable Samples
- Arabidopsis Gene 1.1 ST Array (aragene11st)
Description
Brassinosteroids (BRs) are growth-promoting plant hormones that play a role in abiotic stress responses, but molecular modes that enable this activity remain largely unknown. Here we show that BRs participate in the regulation of freezing tolerance. BR signaling-defective mutants of Arabidopsis thaliana were hypersensitive to freezing before and after cold acclimation. The constitutive activation of BR signaling, in contrast, enhanced freezing resistance. Evidence is provided that the BR-controlled basic helixloophelix transcription factor CESTA (CES) can contribute to the constitutive expression of the C-REPEAT/DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR (CBF) transcriptional regulators that control cold responsive (COR) gene expression. In addition, CBF-independent classes of BR-regulated COR genes are identified that are regulated in a BR- and CES-dependent manner during cold acclimation. A model is presented in which BRs govern different cold-responsive transcriptional cascades through the posttranslational modification of CES and redundantly acting factors. This contributes to the basal resistance against freezing stress, but also to the further improvement of this resistance through cold acclimation.
Publication Title
Brassinosteroids participate in the control of basal and acquired freezing tolerance of plants.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
RNA-Seq analysis of SSA treated cells Overall design: HeLa cells, nuclear and cytoplasmic fractions, treated with SSA or MeOH
Publication Title
Global analysis of pre-mRNA subcellular localization following splicing inhibition by spliceostatin A.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
In mouse models, the bromodomain PHD finger transcription factor (BPTF) chromatin remodeling subunit in tumor cells suppresses natural killer (NK) cell antitumor activity.
Publication Title
BPTF Depletion Enhances T-cell-Mediated Antitumor Immunity.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Depleting the NURF chromatin remodeling complex results in enhanced antitumor immunity using mouse tumor models syngenic to two strain backgrounds.
Publication Title
BPTF Depletion Enhances T-cell-Mediated Antitumor Immunity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Overarching aim is to achieve a greater understanding of the control of progenitor cells within the adult human retina within the normal and diseased retinal microenvironment. Specifically we will assess via our experimental designs: (i) the control of CD133+ retinal cell populations that display mitotic potential and differentiation and
Publication Title
CD133+ adult human retinal cells remain undifferentiated in Leukaemia Inhibitory Factor (LIF).
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Microtubule actin crosslinking factor 1 (Macf1) plays a role in coordinated actions of actin and microtubules in multiple cellular processes. Here we show that Macf1 is also critical for ciliogenesis in multiple cell types. Ablation of Macf1 in the developing retina abolishes ciliogenesis and basal bodies fail to dock to ciliary vesicles or migrate apically. Photoreceptor polarity is randomized while inner retinal cells laminate correctly, suggesting that photoreceptor maturation is guided by polarity cues provided by cilia. Deletion of Macf1 in adult photoreceptors caused reversal of basal body docking and loss of outer segments, reflecting a continuous requirement for Macf1 function. Macf1 was also shown to interact with ciliary proteins Mkks and Talpid3. We propose that a disruption of trafficking across microtubles to actin filaments underlies the ciliogenesis defect in cells lacking Macf1, and that Mkks and Talpid3 are involved in the coordination of microtubule and actin interactions. Overall design: RNA was isolated from confluent mouse embryonic fibroblasts (3 clones per genotype). MEFs where generated from Macf1flox/flox and Macf1flox/+ mice, and immortalized via transfection with the SV40 large T antigen. Cells were grown to 75% confluency and treated with AAV8-CMV-Cre (1.2x10e13vg/ml) overnight. Single cell colonies were generated and recombination for the Macf1 knockout allele (Macf1-/-) and heterozygous control (Macf1-/+) was confirmed by sequencing. Loss of protein expression was confirmed by western blot. Cells were grown to confluency and serum starved on gelatin coated glass coverslips prior to fixing and immunostaining as described for the retina.
Publication Title
Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Using gene expression to predict differences in the secretome of human omental vs. subcutaneous adipose tissue.
Sample Metadata Fields
Sex, Specimen part
View Samples