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Mus musculus
36 Downloadable Samples
NextSeq 500
Description
Transcriptional regulation by chromatin is a highly dynamic process directed through the recruitment and coordinated action of epigenetic modifiers and readers of these modifications. Using an unbiased proteomic approach to find interactors of H3K36me3, a modification enriched on active chromatin, here we identify PWWP2A and HDAC2 among the top interactors. PWWP2A and its paralog PWWP2B form a stable complex with NuRD subunits MTA1/2/3:HDAC1/2:RBBP4/7, but not with MBD2/3, p66a/ß, and CHD3/4. PWWP2A competes with MBD3 for binding to MTA1, thus defining a new variant NuRD complex that is mutually exclusive with the MBD2/3-containing NuRD. In mESCs, PWWP2A/B is most enriched at highly transcribed genes. Loss of PWWP2A/B leads to increases in histone acetylation predominantly at highly expressed genes, accompanied by decreases in Pol II elongation. Collectively, these findings suggest a role for PWWP2A/B in regulating transcription through the fine-tuning of histone acetylation dynamics at actively transcribed genes. Overall design: In order to explore the influence of PWWP2A/B on nascent transcription, we isolated the 4sU-labelled nascent transcripts, followed by deep sequencing. Three cell lines, E14, PWWP2A KO, and PWWP2A/B double knockout, and three biological replicates.
Publication Title
A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate transcription at active genes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Epigenetic regulation of gene expression by histone modification has emerged as a major facet of physiologic and disease processes. As a result, there has been intense interest in developing epigenetic therapies leading to the discovery of small molecule agents that target proteins involved in histone modification. Several histone deacetylase (HDAC) inhibitors are now approved drugs for a specialized group of hematologic malignancies but not yet for a wider range of cancer types including solid tumors. One of the conceptual challenges in targeting HDACs is that even selective class I HDAC inhibitors likely impact these deacetylase activities indiscriminately across a range of distinct HDAC-containing multiprotein complexes. Such broad cellular effects may result in a narrow therapeutic window between disease efficacy and toxicity. Among HDAC complexes, the CoREST complex, which includes HDAC1 or its close paralog HDAC2, the scaffolding protein CoREST, and lysine specific demethylase 1 (LSD1) has attracted special interest. Here we report corin2, designed to dually inhibit the CoREST complex major enzymatic activities, lysine specific demethylase 1 (LSD1) and HDACs 1/2. Corin2 is a synthetic hybrid agent derived from the class I HDAC inhibitor (entinostat) and an LSD1 inhibitor (tranylcypromine analog). Enzymologic analysis reveals that corin2 selectively targets the CoREST complex and shows more sustained inhibition of the CoREST complex HDAC activity than entinostat. Cell-based experiments demonstrate that corin2 exhibits a superior anti-proliferative profile against several melanoma lines compared to its parent monofunctional HDAC and LSD1 inhibitors (alone or in combination) but is less toxic to non-cancerous primary human melanocytes. Transcriptomics analysis shows that corin2 is a more powerful inducer of tumor suppressor genes relative to the parent HDAC and LSD1 compounds (alone or in combination). Genetic knockdown of CoREST or LSD1 in cancer cell lines abolishes the differences in potency of corin2 vs. entinostat, suggesting that corin2's favorable pharmacologic effects rely on an intact CoREST complex. Corin2 was also effective in slowing tumor growth in a melanoma mouse xenograft model. These studies highlight the promise of a new class of two-pronged hybrid agents that selectively target particular epigenetic regulatory complexes and offer unique therapeutic opportunities.
Publication Title
Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
WT mice and Nfkb/p65 S534A were exposed to 1mg/kg LPS and their gene expression measured.
Publication Title
Negative regulation of NF-κB p65 activity by serine 536 phosphorylation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
WT mice and Nfkb/p65 S534A were exposed to 1g/kg LPS and their gene expression measured.
Publication Title
Negative regulation of NF-κB p65 activity by serine 536 phosphorylation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression of hepatocyt-specific knockout of Pten and of Pten and Tgfbr2 in mice
Publication Title
Epithelial Transforming Growth Factor-β Signaling Does Not Contribute to Liver Fibrosis but Protects Mice From Cholangiocarcinoma.
Sample Metadata Fields
Sex, Specimen part
View Samples
GSE3865- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Transcript profiling analysis of csn4-1 light grown mutant seedlings compared to wild type using Arabidopsis ATH1 GeneChip array
Publication Title
Characterization of the VIER F-BOX PROTEINE genes from Arabidopsis reveals their importance for plant growth and development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gene expression of periphereal blood lymphocytes (PBLs) of patients with metastatic renal cell carcinoma pre and post immunotherapy was accessed and pre therapy gene expression was compared to PBL gene expression of healthy volunteers
Publication Title
Gene expression profile of peripheral blood lymphocytes from renal cell carcinoma patients treated with IL-2, interferon-α and dendritic cell vaccine.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Rattus norvegicus
- 11 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Transplanting renal allografts represents the major curative treatment of chronic renal failure. Despite recent advances in immunosuppressive therapy, long-term survival of allografts remains a major clinical problem. Kidney function depends in part on transport proteins such as MRP2 (ABCC2) which facilitates renal secretion of amphiphilic exogenous and endogenous compounds. Inherited variants of genes not related to the immune system have been shown to modify the outcome after renal transplantation. We investigated whether ABCC2 gene variants in the donor kidney affect renal graft function.
Publication Title
Multidrug resistance-related protein 2 genotype of the donor affects kidney graft function.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression of mouse hepatic stellate cells was characterized under the following conditions:
Publication Title
Deactivation of hepatic stellate cells during liver fibrosis resolution in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Brain perivascular cells have been recently identified as new mesodermal cell type of the human brain.
Publication Title
Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.
Sample Metadata Fields
Specimen part
View Samples