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accession-icon GSE22186
Phosphorylation of p53 Serine 46 contributes to target gene selectivity of p53
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Role of p53 serine 46 in p53 target gene regulation.

Sample Metadata Fields

Specimen part, Cell line, Compound

View Samples
accession-icon GSE22184
Phosphorylation of p53 Serine 46 contributes to target gene selectivity of p53 (Exon)
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)

Description

The tumor suppressor p53 plays a crucial role in cellular growth control inducing a plethora of cellular response pathways. The molecular mechanisms that discriminate between the distinct p53-responses towards different stress treatments have remained largely elusive. Here, we have analyzed the p53-regulated pathways induced by two chemotherapeutical treatments, Actinomycin D inducing growth arrest and Etoposide resulting in apoptosis. We found that the genome-wide p53-binding patterns are almost identical upon both treatments notwithstanding transcriptional differences that we observed in genome-wide transcriptome analysis. To assess the role of post-translational modifications in target gene choice and activation we investigated the extent of phosphorylation of Serine 46 of p53 bound to DNA (p53-pS46), a modification that has been linked to apoptosis-pathways, and the extent of phosphorylation of Serine 15 (p53-pS15), a general p53-activation mark. Interestingly, the overall extent of S46 phosphorylation of p53 bound to DNA is considerably higher in cells directed towards apoptosis while the degree of phosphorylation at S15 of DNA bound p53 remains highly similar upon both treatments. Moreover, our data suggest that, following different chemotherapeutical treatments, the extent of chromatin-associated p53 phosphorylated at S46 but not at pS15 is higher on certain apoptosis related target genes, including the BAX and PUMA genes. These data provide evidence that cell fate decisions are not made primarily on the level of general p53 DNA-binding, but possibly through post-translational modifications of chromatin bound p53.

Publication Title

Role of p53 serine 46 in p53 target gene regulation.

Sample Metadata Fields

Specimen part, Cell line

View Samples
accession-icon GSE42188
Adenoviral shRNA-based knockdown of hepatic Hnf1b (Ad-shHnf1b)
  • organism-icon Mus musculus
  • sample-icon 7 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Insulin resistance represents a hallmark during the development of type 2 diabetes mellitus (T2D) and in the pathogenesis of obesity-associated disturbances of glucose and lipid metabolism 1,2,3. MicroRNA (miR)-dependent posttranscriptional gene silencing has recently been recognized to control gene expression in disease development and progression including that of insulin-resistant T2D. MiRs, whose deregulation alters hepatic insulin sensitivity include miR-143, miR-181 and miR-103/107. Here we report that expression of miR-802 is increased in liver of two obese mouse models and of obese human subjects. Inducible transgenic overexpression of miR-802 in mice causes impaired glucose tolerance and attenuates insulin sensitivity, while reduction of miR-802 expression improves glucose tolerance and insulin action. We identify Hnf1b as a target of miR-802-dependent silencing and shRNA-mediated reduction of Hnf1b in liver causes glucose intolerance, impairs insulin signaling and promotes hepatic gluconeogenesis. In turn, hepatic overexpression of Hnf1b improves insulin sensitivity in db/db mice. Thus, the present study defines a critical role for deregulated expression of miR-802 in the development of obesity-associated impairment of glucose metabolism via targeting Hnf1b and assigns Hnf1b an unexpected role in the control of hepatic insulin sensitivity.

Publication Title

Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b.

Sample Metadata Fields

Sex, Specimen part

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accession-icon SRP147553
Splicing and epigenetic factors jointly regulate epidermal differentiation
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

We report the effects of silencing SRSF1 or ZMAT2 in human epidermal stem cells on the transcriptome of epidermal stem cells. We found that silencing ZMAT2 or SRSF1 affects global splicing, however, ZMAT2 seems to regulate splicing of a smaller more specific subset of genes. Overall design: RNA-sequencing data following silencing SRSF1 or ZMAT2

Publication Title

Splicing and Chromatin Factors Jointly Regulate Epidermal Differentiation.

Sample Metadata Fields

Specimen part, Subject, Time

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accession-icon SRP155035
STVI-120 Induction of differentiation in human epidermal stem cells followed by differential splicing analysis
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

We report the effects of induction of differentiation in human epidermal stem cells on the splicing of the transcriptome. Overall design: RNA-sequencing data following induction of differentiation in human epidermal stem cells

Publication Title

Splicing and Chromatin Factors Jointly Regulate Epidermal Differentiation.

Sample Metadata Fields

Specimen part, Treatment, Subject

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accession-icon GSE18314
High-level furfural resistance in S. cerevisiae is based on NADPH-dependent reduction by at least two oxireductases
  • organism-icon Saccharomyces cerevisiae
  • sample-icon 13 Downloadable Samples
  • Technology Badge Icon Affymetrix Yeast Genome 2.0 Array (yeast2)

Description

Resistance of Saccharomyces cerevisiae to high furfural concentration is based on NADPH-dependent reduction by at least two oxireductases.

Publication Title

Resistance of Saccharomyces cerevisiae to high concentrations of furfural is based on NADPH-dependent reduction by at least two oxireductases.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE20910
Expression data from Down syndrome and non-Down syndrome pediatric acute lymphoblastic leukemia cases
  • organism-icon Homo sapiens
  • sample-icon 47 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Gene expression profiling (GEP) can reveal characteristic signatures associated with distinct biologic subtypes of acute lymphoblastic leukemia (ALL).

Publication Title

Genomic profiling in Down syndrome acute lymphoblastic leukemia identifies histone gene deletions associated with altered methylation profiles.

Sample Metadata Fields

Specimen part, Disease

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accession-icon GSE21094
Genomic profiling in Down syndrome pediatric acute lymphoblastic leukemia
  • organism-icon Homo sapiens
  • sample-icon 3 Downloadable Samples
  • Technology Badge Icon

Description

Patients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have distinct clinical and biological features. Whereas most DS-ALL cases lack the sentinel cytogenetic lesions that guide risk assignment in childhood ALL, JAK2 mutations and CRLF2 overexpression are highly enriched. To further characterize the unique biology of DS-ALL, we performed genome-wide profiling of 58 DS-ALL and 35 non-Down syndrome (NDS) ALL cases by DNA copy number, loss of heterozygosity, gene expression, and methylation analyses. We report novel deletions within the 6p22 histone gene cluster as significantly more frequent in DS-ALL, occurring in 12 DS (24%) and only a single NDS case (3%) (Fishers exact p = 0.013). Homozygous deletions yielded significantly lower histone expression levels, and were associated with higher methylation levels, distinct spatial localization of methylated promoters, and enrichment of highly methylated genes for specific pathways and transcription factor binding motifs. Gene expression profiling identified CRLF2 overexpression in nearly half DS-ALL cases, and supervised analysis identified an associated 39-gene signature. However, no expression signature was identified for DS-ALL overall, nor for histone status, suggesting that DS-ALL constitutes several, heterogeneous molecular entities. Characterization of pathways associated with histone deletions and high CRLF2 expression may identify opportunities for novel targeted interventions.

Publication Title

Genomic profiling in Down syndrome acute lymphoblastic leukemia identifies histone gene deletions associated with altered methylation profiles.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE1009
Diabetic nephropathy
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U95 Version 2 Array (hgu95av2)

Description

Gene expression profiling in glomeruli from human kidneys with diabetic nephropathy

Publication Title

Gene expression profiling in glomeruli from human kidneys with diabetic nephropathy.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon E-MTAB-912
Spermidine Yeast Aging Array
  • organism-icon Saccharomyces cerevisiae
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Yeast Genome 2.0 Array (yeast2)

Description

Administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extends the lifespan of various model organisms including yeast, flies and worms. In ageing yeast, spermidine treatment triggeres epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), leading to induction of autophagy and thereby suppressing oxidative stress and necrosis. In order to further characterize the effects by spermidine supplementation of aging yeast cultures and to understand how global histone deacetylation affects gene transcription during aging, Affymetrix-based microarray analyses of three day old as well as ten day old cultures with and without administration of spermidine was performed.

Publication Title

Induction of autophagy by spermidine promotes longevity.

Sample Metadata Fields

Age, Compound, Time

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

fund-icon Fund the CCDL

Developed by the Childhood Cancer Data Lab

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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