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GSE81267
Homo sapiens
33 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Polycomb repressive complex (PRC) 2, containing minimally EZH2, EED and Suz12, is the H3 lysine 27 methyltransferase playing pivotal roles in transcriptional regulation. EZH2 is the catalytic subunit, and H3K27me3 activates PRC2 through binding EED to propagate the repressive mark. Cofactor SAM-competitive (SAM-C) PRC2 inhibitors (PRC2is) have been discovered to treat lymphoma and rhabdoid tumors. Here we report the discovery of EED226, a potent and selective PRC2i directly binding to the H3K27me3 pocket of EED. Upon binding, EED226 induces conformational change in EED protein. Interestingly, it inhibits both the basal and the H3K27me3-stimulated PRC2 activities. Furthermore, EED226 selectively pulled down the endogenous PRC2 complex from human cell lysates, specifically modulates H3K27 methylation and target genes similarly as SAM-C PRC2 inhibitors, and effectively regresses human lymphoma xenograft tumor in mouse. More importantly, EED226 potently inhibits the SAM-C inhibitor-resistant PRC2 and synergizes with SAM-C PRC2i in cell proliferation blocking. Together, EED226 is an inhibitor of PRC2 with a novel mechanism and represent a potential complementary strategy for PRC2-targeted cancer therapy.
Publication Title
An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 208 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Chronic obstructive pulmonary disease is a smoking-related disease that lacks effective therapies due partly to the poor understanding of disease pathogenesis. The aim of this study was to identify molecular pathways which could be responsible for the damaging consequences of smoking. To do this, we employed recently described bioinformatic methods to analyze differences in global gene expression, which we then related to the pathological changes induced by cigarette smoke (CS). Sprague-Dawley rats were exposed to whole-body CS for 1 day and for various periods up to 8 months.
Publication Title
Comprehensive gene expression profiling of rat lung reveals distinct acute and chronic responses to cigarette smoke inhalation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Age-related frailty may in part be due to a decreased competency in skeletal muscle regeneration. The role of the closely related TGFbeta amily molecules myostatin and GDF11 in regeneration is unclear. The commercially available antibody which in a prior report was used to demonstrate an age-related decrease in GDF11 was found to detect both GDF11 and myostatin, and with this reagent it appears that the combination of GDF11 and myostatin increases with age in serum. Mechanistically, GDF11 and myostatin induce SMAD2/3 phosphorylation, and both inhibit myoblast differentiation and regulate identical downstream signaling. GDF11 injected into adult mice in a model of regeneration induces an increase in smaller fibers and a decrease in satellite cell expansion. There are no signs of benefit from GDF11 to regeneration. Thus, GDF11 appears to be an age-associated myokine that inhibits muscle differentiation, and is thus a target for blockade to treat frailty
Publication Title
GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration.
Sample Metadata Fields
Treatment, Time
View Samples- Mus musculus, Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression upon DOT1L inhibition, or Menin inhibition, or a combination of DOT1L and Menin inhibiting agents, was assessed in several MLL-rearranged human cell lines and a mouse model of MLL-AF9 leukemia.
Publication Title
Complementary activities of DOT1L and Menin inhibitors in MLL-rearranged leukemia.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Utilizing glycerol and cardiotoxin (CTX) injections in the tibialis anterior muscles of M. musculus provides models of skeletal muscle damages followed by skeletal muscle regeneration. In particular, glycerol-induced muscle regeneration is known to be associated with ectopic adipogenesis. We characterized genome-wide expression profiles of tibialis anterior muscles from wild-type mice injured by either glycerol or CTX injection. Our goal was to detect gene expression changes during the time course of glycerol-induced and CTX-induced muscle regeneration models, that can lead to ectopic adipocyte accumulation.
Publication Title
Genomic profiling reveals that transient adipogenic activation is a hallmark of mouse models of skeletal muscle regeneration.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 37 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The RPMI-8226 human multiple myeloma cell line was stably infected with either a validated shRNA against BMI1 or a control shRNA. RNA was prepared from these lines, +/- doxycycline induction and at various time points post-induction. Samples were hybridized on the Affymetrix U133plus2 human genome expression microarray.
Publication Title
The Polycomb group protein Bmi-1 is essential for the growth of multiple myeloma cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 42 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The series were performed to study the changes in gene expression upon diploidization of KBM7 cancer (CML) cell line. The line can exist either as a clone with 24 chromosomes (nearly haploid) or with
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 38 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Low aerobic exercise capacity increases susceptibility to smoking-induced inflammation and tissue damage
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Oxidative stress as a result of cigarette smoking is an important etiological factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), a chronic steroid-insensitive inflammatory disease of the airways. The activity of the transcriptional co-repressor Histone deacetylase-2 (HDAC2) is dramatically reduced in COPD and cells exposed to oxidative stress or cigarette smoke. Moreover, curcumin (diferuloylmethane), a dietary polyphenol, at concentrations upto 1uM specifically restores cigarette smoke extract (CSE)- or oxidative stress- impaired HDAC2 activity. The aim of this study was to therefore identify any links through those gene sets that are affected by oxidative stress and subsequent treatment with curcumin in order to determine whether or not this could explain the impact of curcumin on restoration of oxidant impaired HDAC2 transcriptional co-repressor activity.
Publication Title
Curcumin restores corticosteroid function in monocytes exposed to oxidants by maintaining HDAC2.
Sample Metadata Fields
No sample metadata fields
View Samples