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accession-icon SRP042961
X-chromosome dynamics revealed by the RNA interactome and chromosomal binding of CTCF
  • organism-icon Mus musculus
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon

Description

CTCF is a master regulator that plays a role in genome architecture and gene expression. A key aspect of CTCF’s mechanism involves bringing together distant genetic elements for intra- and inter-chromosomal interactions. Evidence from epigenetic processes, such as X-chromosome inactivation (XCI), suggests that CTCF may carry out its functions through interacting RNAs. Using genome-wide approaches to investigate the relationship between CTCF’s RNA interactome and its epigenomic landscape, here we report that CTCF interacts with thousands of transcripts in mouse embryonic stem cells (mESC), many in close proximity to CTCF’s genomic binding sites. Biochemical analysis demonstrates that CTCF is a high-affinity RNA binding protein that contacts RNA directly and specifically. In the XCI model, CTCF binds the active and inactive X-chromosomes allele-specifically. At the X-inactivation center, Tsix RNA binds CTCF and targets CTCF to a region associated with X-chromosome pairing. Our work implicates CTCF-RNA interactions in long-range chromosomal interactions in trans and adds a new layer of complexity to CTCF regulation. The genome-wide datasets reported here will provide a useful resource for further study of CTCF-mediated epigenomic regulation. Overall design: CTCF RNA interactome was identified by UV-crosslinking and immunoprecipitation followed by high-throughput sequencing (CLIP-seq), and was compared to CTCF''s epigenomic landscape as obtained by chromatin immunoprecipitation (ChIP-seq).

Publication Title

Locus-specific targeting to the X chromosome revealed by the RNA interactome of CTCF.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE35525
Pivotal role of HMGA1 gene signature in highly metastatic breast cancer
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Analysis of MDA-MB-231 breast cancer cells depleted for High Mobility Group A1 (HMGA1) using siRNA. HMGA1 is involved in invasion and metastasis in breast cancer cells. Results identify the specific transcriptional program induced by HMGA1 in highly metastatic breast cancer cells.

Publication Title

HMGA1 promotes metastatic processes in basal-like breast cancer regulating EMT and stemness.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon GSE30700
The Bromodomain protein Brd4 Insulates Chromatin from DNA Damage Signaling through Acetyl-Lysine Binding
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A 2.0 Array (hgu133a2)

Description

DNA damage activates a complex signaling network in cells that blocks cell cycle progression, recruits factors involved in DNA repair, and/or triggers programs that control senescence or programmed cell death. Alterations in chromatin structure are known to be important for the initiation and propagation of the DNA damage response, although the molecular details are unclear. We investigated the role of chromatin structure in the DNA damage response by monitoring multiple timedependent checkpoint signaling and response events with a high-content multiplex image-based RNAi screen of chromatin modifying and interacting genes. We discovered that Brd4, a double bromodomain-containing protein, functions as an endogenous inhibitor of DNA damage signaling by binding to acetylated histones at sites of open chromatin and altering chromatin accessibility. Loss of Brd4 or disruption of acetyl-lysine binding results in an increase in both the number and size of radiation-induced !H2AX nuclear foci while overexpression of a Brd4 splice isoform completely suppresses !H2AX formation, despite equivalent double strand break formation. Brd4 knock-down cells displayed altered chromatin structure, prolonged cell cycle checkpoint arrest and enhanced survival after irradiation, while overexpression of Brd4 isoform B results in enhanced radiationinduced lethality. Brd4 is the target of the t(15;19) chromosomal translocation in a rare form of cancer, NUT Midline Carcinoma. Acetyl lysine-bromodomain interactions of the Brd4-NUT fusion protein suppresses !H2AX foci in discrete nuclear compartments, rendering cells more radiosensitive, mimicking overexpression of Brd4 isoform B. NUT Midline Carcinoma is sensitive to radiotherapy, however tumor material from this rare cancer is scarce. We therefore investigated Brd4 expression in another human cancer commonly treated with radiotherapy, glioblastoma multiforme, and found that expression of Brd4 isoform B correlated specifically with treatment response to radiotherapy. These data implicate Brd4 as an endogenous insulator of DNA damage signaling through recognition of epigenetic modifications in chromatin and suggest that expression of the Brd4 in human cancer can modulate the clinical response to DNA-damaging cancer therapy.

Publication Title

The bromodomain protein Brd4 insulates chromatin from DNA damage signalling.

Sample Metadata Fields

Cell line

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accession-icon GSE36975
Expression of Human nave B cell priming for plasma cell differentiation
  • organism-icon Homo sapiens
  • sample-icon 24 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

To explore events that govern the differentiation of human nave B cells (NBCs) into memory B cells and plasma cells (PCs), we designed an in vitro 2-step culture model leading non-switched NBC precursors to differentiate into two cell compartments: CD20loCD38hi and CD20+CD38+.

Publication Title

IL-2 requirement for human plasma cell generation: coupling differentiation and proliferation by enhancing MAPK-ERK signaling.

Sample Metadata Fields

Specimen part, Subject, Time

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accession-icon GSE72332
Gene expression data of human mesenchymal stromal cells, fibroblasts and hematopoietic progenitors
  • organism-icon Homo sapiens
  • sample-icon 15 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Exon 1.0 ST Array [CDF: genemapperhumanexon1.0cdf_3.0 (huex10st)

Description

The data presented is intended to analyse the changes in the expression profiles of human MSCs (Mesenchymal Stromal/Stem Cells) associated to different tissue specific stimulus.

Publication Title

Insights into the human mesenchymal stromal/stem cell identity through integrative transcriptomic profiling.

Sample Metadata Fields

Specimen part

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accession-icon GSE93529
Mechanical cues control mutant p53 stability through a Mevalonate/RhoA axis
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

To investigate the genes differentially expressed upon plating on top of matrixes with different stiffness, we compared the expression profiles of MDA-MB-231 breast cancer cells plated on a stiff substrate (plastic) with the same cells plated on a soft substrate (hydrogels 0.7 kPa).

Publication Title

Mechanical cues control mutant p53 stability through a mevalonate-RhoA axis.

Sample Metadata Fields

Cell line

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accession-icon GSE21547
Angio-modulation in endothelial cells: an unexpected role of desmoglein-2 in regulating actin dynamics and its relevance to angiogenesis deregulation in systemic sclerosis
  • organism-icon Homo sapiens
  • sample-icon 5 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Gene expression study of DSG2 silenced human microvascular endothelial cells

Publication Title

Desmoglein-2-integrin Beta-8 interaction regulates actin assembly in endothelial cells: deregulation in systemic sclerosis.

Sample Metadata Fields

Specimen part

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accession-icon GSE26262
Pin1/mutant-p53 jointly controlled genes
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A 2.0 Array (hgu133a2)

Description

To investigate the specific gene expression program by which mutant-p53 and Pin1 control invasion and metastasis in breast cancer cells, we compared the transcriptomic profile of control, mutant-p53 depleted or Pin1 depleted MDA-MB-231 cells.

Publication Title

A Pin1/mutant p53 axis promotes aggressiveness in breast cancer.

Sample Metadata Fields

Cell line

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accession-icon SRP057644
Proteasome machinery is instrumental in a common gain-of-function program of the p53 missense mutants in cancer.
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2000

Description

Mutant p53 proteins, resulting from the missense mutations of the TP53 tumor suppressor gene, possess gain-of-function activities and are among the most robust oncoproteins in human tumors. They are potentially important therapeutic targets. No studies to date have distinguished common, therapeutically relevant mutant p53 gain-of-function effects from effects specific to different mutant variants and cell backgrounds. here we performed RNA-seq analysisin MDA-MB-231 (R280K) upon silencing TP53 or the control siRNA. Overall design: MDA-MB-231 (R280K) cell line was transfected with control or p53 siRNA.So The study comprises one experimental cell line,in triplicate.

Publication Title

Proteasome machinery is instrumental in a common gain-of-function program of the p53 missense mutants in cancer.

Sample Metadata Fields

No sample metadata fields

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accession-icon E-MEXP-1563
Transcription profiling of rat mixed-tissue RNA samples using different labeling protocols
  • organism-icon Rattus norvegicus
  • sample-icon 24 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Expression 230A Array (rae230a), Affymetrix Rat Genome 230 2.0 Array (rat2302)

Description

At one site (#10), three different batches of MTRRM (see E-TABM-16), were labeled with two different kits (Enzo and Affymetrix) and hybridized to two different Affymetrix Arrays (RAE230A and RAE230_2).

Publication Title

Use of diagnostic accuracy as a metric for evaluating laboratory proficiency with microarray assays using mixed-tissue RNA reference samples.

Sample Metadata Fields

Sex, Age

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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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