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accession-icon GSE47179
Effects of KAT2B and WDR5 depletion on hepatocyte gene expression
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

During fasting, increases in circulating pancreatic glucagon maintain glucose balance by up-regulating hepatic gluconeogenesis. Triggering of the cAMP pathway stimulates the gluconeogenic program through the phosphorylation of CREB and via the de-phosphorylation of the CREB coactivator CRTC2. Hormonal and nutrient signals are also thought to modulate gluconeogenic genes by promoting epigenetic changes that facilitate assembly of the transcriptional machinery, although the nature of these modifications is unclear. Here we show that histone H3 acetylation at Lys 9 (H3K9Ac) is elevated over gluconeogenic genes during fasting and in diabetes, where it contributes to increases in hepatic glucose production. Following its dephosphorylation, CRTC2 promoted increases in H3K9Ac by mediating the recruitment of the lysine acetyltransferase 2B (KAT2B) and WD repeat-containing protein 5 (WDR5), a core subunit of histone methyltransferase (HMT) complexes. In turn, KAT2B and WDR5 stimulated the gluconeogenic program through a self-reinforcing cycle whereby increases in H3K9Ac further potentiated CRTC2 occupancy at CREB binding sites. Breaking this cycle, by depletion of KAT2B or WDR5, decreased gluconeogenic gene expression. As administration of a small molecule KAT2B antagonist lowered circulating blood glucose concentrations in insulin resistance, our results demonstrate how this enzyme may be a useful target for diabetes treatment.

Publication Title

Glucagon regulates gluconeogenesis through KAT2B- and WDR5-mediated epigenetic effects.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon GSE14363
Expression data from adipocytes and white adipose tissue of mice maintained on normal chow or high fat diet
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Description

We studied the role of the cAMP responsive factor CREB in promoting insulin resistance following its activation in adipose under obese conditions

Publication Title

Adipocyte CREB promotes insulin resistance in obesity.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE13143
Expression data from 3T3-MEFs derived from wild-type and SMRT RID mutant mice
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

SMRT (silencing mediator of retinoid and thyroid hormone receptors) is recruited by numerous transcription factors to mediate lineage and signal dependent transcriptional repression. We generated a knock-in mutation in the receptor interaction domain (RID) of SMRT (SMRTmRID) that solely disrupts its interaction with nuclear hormone receptors. SMRTmRID-derived 3T3-MEFs display a dramatically increased adipogenic capacity and accelerated differentiation rate. We measured global gene expression in wild-type versus SMRTmRID-derived 3T3-MEFs in the undifferentiated state to examine which pathways were altered. Our results demonstrate that SMRT-RID dependent repression is a key determinant of the adipogenic set point.

Publication Title

SMRT repression of nuclear receptors controls the adipogenic set point and metabolic homeostasis.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE28199
prdm1a mutant vs. wild type
  • organism-icon Danio rerio
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Zebrafish Genome Array (zebrafish)

Description

The PR domain containing 1a, with ZNF domain factor, gene prdm1a plays an integral role in the development of a number of different cell types during vertebrate embryogenesis, including neural crest cells, Rohon-Beard (RB) sensory neurons and the cranial neural crest-derived craniofacial skeletal elements. To better understand how Prdm1a regulates the development of various cell types in zebrafish, we performed a microarray analysis comparing wild type and prdm1a mutant embryos and identified a number of genes with altered expression in the absence of prdm1a. Rescue analysis determined that two of these, sox10 and islet1, lie downstream of Prdm1a in the development of neural crest cells and Rohon-Beard neurons, respectively. In addition, we identified a number of other novel downstream targets of Prdm1a that may be important for the development of diverse tissues during zebrafish embryogenesis.

Publication Title

prdm1a Regulates sox10 and islet1 in the development of neural crest and Rohon-Beard sensory neurons.

Sample Metadata Fields

Age, Specimen part

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accession-icon GSE29955
Expression data from cells with siRNA-mediated knockdown of OPG and from HVSMCs incubated with RANKL or TRAIL
  • organism-icon Homo sapiens
  • sample-icon 18 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A 2.0 Array (hgu133a2)

Description

We used microarrays to assess gene expression changes in cells with siRNA-mediated knockdown of OPG compared to normal cells. Furthermore, we used microarrays to assess gene expression in cells treated with either RANKL or TRAIL compared to vehicle-treated cells.

Publication Title

No influence of OPG and its ligands, RANKL and TRAIL, on proliferation and regulation of the calcification process in primary human vascular smooth muscle cells.

Sample Metadata Fields

Specimen part, Treatment

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accession-icon SRP135264
Transcriptomic profiling of trigeminal nucleus caudalis (TNC) and spinal cord dorsal horn (SC)
  • organism-icon Rattus norvegicus
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

RNA-Sequencing of the trigeminal nucleus caudalis and spinal cord, dorsal horn in male naive rats (Wistar Han) of 10 weeks old Overall design: 6 naive rats were killed after 2 weeks of arrival, both trigeminal nucleus caudalis and spinal cord dorsal horn were dissected using laser capture microdissection of each rat.

Publication Title

Transcriptomic profiling of trigeminal nucleus caudalis and spinal cord dorsal horn.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE20916
Modeling oncogenic signaling in colon tumors by multidirectional analyses of microarray data
  • organism-icon Homo sapiens
  • sample-icon 144 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Background. Most colorectal cancers (CRC) arise in a progression through adenoma to carcinoma phenotypes as a consequence of altered genetic information. Clinical progression of CRC may occur in parallel with distinctive signaling alterations. We designed multidirectional analyses integrating microarray-based data with biostatistics and bioinformatics to elucidate the signaling and metabolic alterations underlying CRC development in the adenoma-carcinoma sequence. Methodology/Principal Findings. Studies were performed on normal mucosa, adenoma, and CRC samples obtained during surgery or colonoscopy. Collections of cryostat sections prepared from the tissue samples were evaluated by a pathologist to control the relative cell type content. RNA was isolated from 105 macro- and 40 microdissected specimens. The measurements were done using Affymetrix GeneChip HG-U133plus2, and probe set data were generated using two normalization algorithms: MAS5 and GCRMA with LVS. The data were evaluated using pair-wise comparisons and data decomposition into SVD modes. The method selected for the functional analysis used the Kolmogorov-Smirnov test. Based on a consensus of the results obtained by two tissue handling procedures, two normalization algorithms, and two probe set sorting criteria, we identified six KEGG signaling and metabolic pathways (cell cycle, DNA replication, p53 signaling pathway, purine metabolism, pyrimidine metabolism, and RNA polymerase) that are significantly altered in both macro- and microdissected tumor samples compared to normal colon. On the other hand, pathways altered between benign and malignant tumors were identified only in the macrodissected tissues. Conclusion/Significance. Multidirectional analyses of microarray data allow the identification of essential signaling alterations underlying CRC development. Although the proposed strategy is computationally complex and laborintensive, it may reduce the number of false results.

Publication Title

Modeling oncogenic signaling in colon tumors by multidirectional analyses of microarray data directed for maximization of analytical reliability.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon GSE109792
Gene Expression during Panobinostat Dosing
  • organism-icon Homo sapiens
  • sample-icon 59 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Transcriptome Array 2.0 (hta20)

Description

A clinical study evaluating the dosing of an oral HDACi panobinostat in patient infected with HIV-1. Dosing was 20 mg orally, 3 times weekly, every other week for a total of 8 weeks.

Publication Title

Treatment of HIV-Infected Individuals with the Histone Deacetylase Inhibitor Panobinostat Results in Increased Numbers of Regulatory T Cells and Limits <i>Ex Vivo</i> Lipopolysaccharide-Induced Inflammatory Responses.

Sample Metadata Fields

Sex

View Samples
accession-icon GSE21033
Timecourse analysis of gene expression by murine bone marrow-generated dendritic cells following treatment with Poly I:C
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

BACKGROUND: Dendritic cells (DC) play a central role in primary immune responses and become potent stimulators of the adaptive immune response after undergoing the critical process of maturation. Understanding the dynamics of DC maturation would provide key insights into this important process. Time course microarray experiments can provide unique insights into DC maturation dynamics. Replicate experiments are necessary to address the issues of experimental and biological variability. Statistical methods and averaging are often used to identify significant signals. Here a novel strategy for filtering of replicate time course microarray data, which identifies consistent signals between the replicates, is presented and applied to a DC time course microarray experiment.

Publication Title

Dynamics of dendritic cell maturation are identified through a novel filtering strategy applied to biological time-course microarray replicates.

Sample Metadata Fields

Specimen part

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accession-icon GSE35382
Comparison of gene expression profiles of HT29 cells treated with Instant Caffeinated Coffee or Caffeic Acid versus control.
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

A summary of the work associated to these microarrays is the following:

Publication Title

Coffee polyphenols change the expression of STAT5B and ATF-2 modifying cyclin D1 levels in cancer cells.

Sample Metadata Fields

Cell line, Treatment

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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)

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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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