The bromodomain and extra-terminal domain (BET) proteins are promising drug targets for cancer and immune diseases. However, BET inhibition effects have been studied more in the context of bromodomain-containing protein 4 (BRD4) than BRD2, and the BET protein association to histone H4-hyperacetylated chromatin is not understood at the genome-wide level. Here, we report transcription start site (TSS)-resolution integrative analyses of ChIP-seq and transcriptome profiles in human non-small cell lung cancer (NSCLC) cell line H23. We show that di-acetylation at K5 and K8 of histone H4 (H4K5acK8ac) co-localizes with H3K27ac and BRD2 in the majority of active enhancers and promoters, where BRD2 has a stronger association with H4K5acK8ac than H3K27ac. Although BET inhibition by JQ1 led to complete reduction of BRD2 binding to chromatin, only local changes of H4K5acK8ac levels were observed, suggesting that recruitment of BRD2 does not influence global histone H4 hyperacetylation levels. This finding supports a model in which recruitment of BET proteins via histone H4 hyperacetylation is predominant over hyperacetylation of histone H4 by BET protein-associated acetyltransferases. In addition, we found a remarkable number of BRD2-bound genes, including MYC and its downstream target genes, were transcriptionally upregulated upon JQ1 treatment. Using BRD2-enriched sites and transcriptional activity analysis, we identified candidate transcription factors potentially involved in the JQ1 response in BRD2-dependent and independent manner. Overall design: Lung cancer cell line H23 was treated with JQ1 BET inhibitor. Gene expression profiling by CAGE was performed after 0h, 3h, 6h, 12h and 24h.
JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states.
Specimen part, Treatment, Subject
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MicroRNA-10b pleiotropically regulates invasion, angiogenicity and apoptosis of tumor cells resembling mesenchymal subtype of glioblastoma multiforme.
Specimen part, Cell line
View SamplesAn experimental lung metastasis assay was used to derive an invasive subline of U87 that is metastatic in mice.
MicroRNA-10b pleiotropically regulates invasion, angiogenicity and apoptosis of tumor cells resembling mesenchymal subtype of glioblastoma multiforme.
Specimen part, Cell line
View SamplesMicroRNA-10b may target numerous genes in gliomagenesis. The target genes of miR-10b may differ according to the cellular context.
MicroRNA-10b pleiotropically regulates invasion, angiogenicity and apoptosis of tumor cells resembling mesenchymal subtype of glioblastoma multiforme.
Specimen part, Cell line
View SamplesMiddle cerebral artery occlusion (MCAo) in rat represent the ischemic stroke in human. Rodents subjected to MCAo and treated with venom phospholipase A2 showed reduction in infarct volume after 24hours of stroke.
A secretory phospholipase A2-mediated neuroprotection and anti-apoptosis.
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MicroRNA 144 impairs insulin signaling by inhibiting the expression of insulin receptor substrate 1 in type 2 diabetes mellitus.
Sex, Specimen part, Disease, Disease stage
View SamplesIn this study, we compared the expression profiles of miRNAs in blood samples from Impaired Fasting Glucose (IFG) and T2D male patients. Healthy adult males with no past history of T2D (n=158) and with desirable cholesterol and blood pressure profiles were enrolled in this study. They were then classified according to fasting glucose levels to have T2D, IFG or as healthy controls (CTL), for comparison of miRNA expression profiles. Employing miRNA microarray, we identified signature miRNAs in peripheral blood samples that distinguished IFG and T2D. Eight selected miRNAs were further validated using stem-loop real-time RT-PCR. miR-144 expression was found to be dysregulated in Type 2 Diabetes, wherein its expression was significantly higher than in healthy controls. Insulin receptor substrate 1 (IRS1) has been predicted to be a potential target of miR-144. Consistent with this observation, IRS1 mRNA and protein levels, verified by quantitative real-time PCR and western blotting respectively, were found to be down-regulated.
MicroRNA 144 impairs insulin signaling by inhibiting the expression of insulin receptor substrate 1 in type 2 diabetes mellitus.
Sex
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microRNAs Involved in Regulating Spontaneous Recovery in Embolic Stroke Model.
Sex, Specimen part
View SamplesTo date, miRNA and mRNA expression studies on cerebral ischemia in both human and animal models have focused mainly on acute phase of ischemic stroke. In this study, we present the roles played by microRNAs in the spontaneous recovery phases in cerebral ischemia using rodent stroke models.
microRNAs Involved in Regulating Spontaneous Recovery in Embolic Stroke Model.
Sex, Specimen part
View SamplesMucuna pruriens extract MPE pretreatment may have a direct protective effect on heart (other than immunological neutralization of the venom neurotoxin and phospholipase A2 by the anti-MPE antibodies) that renders the heart more resistant to the toxic action of the venom
Prophylactic effect of Mucuna pruriens Linn (velvet bean) seed extract against experimental Naja sputatrix envenomation: gene expression studies.
Specimen part, Treatment
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