This study investigates how 17-estradiol (E2) both stimulates and inhibits Runx2 in a locus-specific manner. We compare the effects of E2 to those of the Selective Estrogen Receptor Modulators (SERMs) raloxifene (ral) and lasofoxifen (las) and the phytoestrogen peurarin
No associated publication
Sex, Age, Specimen part
View SamplesComparative analysis of RUNX1 and RUNX2 responsiveness in the presence or absence of E2
RUNX1 prevents oestrogen-mediated AXIN1 suppression and β-catenin activation in ER-positive breast cancer.
Cell line, Treatment
View SamplesProfiled the transcriptional response to over-expression Manganese-SOD (MnSOD) in adult Drosophila. A doxycycline-regulated system was employed to induce MnSOD over-expression, resulting in mean and maximal lifespan increases of ~ 20%. Examination of the genome-wide response to this lifespan intervention provided key insights into the molecular basis of aging.
No associated publication
No sample metadata fields
View SamplesIn an acute skin wound, newly released serum growth factors in the wound bed drive lateral migration of human keratinocytes (HKs) to re-epithelialize the wound. However, profiling the migration signal-specific genes has long been challenged by pleiotropic effects of a given growth factor, including proliferation, migration and factor-specific responses. To overcome these technical problems, we 1) took advantage of a unique response of HKs to transforming growth factor-beta (TGFbeta) to selectively suppress growth signal-responding genes and identify motility-specific genes and 2) employed dual stimulation of HKs with TGFalpha and insulin to identify the common genes and eliminate factor-specific genes. Under these conditions, DNA microarray analyses were utilized to study the profiles of both TGFalpha-regualted and insulin-regulated immediate early (IE, 30 min), early (E, 60 min) and delayed early (DE, 120 min) genes.
Profiling motility signal-specific genes in primary human keratinocytes.
No sample metadata fields
View SamplesThe experimental spike-in studies of microarray hybridization conducted by Affymetrix demonstrate a nonlinear response of fluorescence intensity signal to target concentration. It was shown that the Langmuir adsorption isotherm recapitulates a general trend of signal response to concentration. However, this model fails to explain some key properties of the observed signal. In particular, according to the simple Langmuir isotherm, all probes should saturate at the same intensity level. However, this effect was not observed in the publicly available Affymetrix spike-in datasets. In our experimental study, we attempt to account for the unexplained variation in the observed probe intensities using customized fluidics scripts. We explore experimentally the effect of the stringent wash, target concentration, and hybridization time on the final microarray signal.
No associated publication
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
SNF5 is an essential executor of epigenetic regulation during differentiation.
Specimen part, Cell line
View SamplesThe requirements for self-renewal differ between EpiSCs and ES cells and the underlying mechanism is largely unknown. Here we show that mouse EpiSCs can be efficiently derived and robustly propagated even from single cells, using two small-molecule inhibitors: CHIR99021 and XAV939.
No associated publication
Specimen part, Treatment
View SamplesEffect of RUNX1 depletion in the presence or absence of Estradiol
RUNX1 prevents oestrogen-mediated AXIN1 suppression and β-catenin activation in ER-positive breast cancer.
Cell line, Treatment
View SamplesAnalysis of global gene expression by SNF5 level change in human pluripotent and differentiated cells. The core subunit of BAF complex SNF5 is at the nexus of the link between chromatin remodeling and tumor suppression. We demonstrated a role for the remodeler SNF5 as a key executor in regulating pluripotency gene networks during differentiation by using loss and gain of function experiments followed by gene-expression arrays.
SNF5 is an essential executor of epigenetic regulation during differentiation.
Specimen part, Cell line
View SamplesDNA methylation, histone modifications, and nucleosomal occupancy collaborate to cause silencing of tumor related genes in cancer. The development of drugs that target these processes is therefore important for cancer therapy. Inhibitors of DNA methylation and histone deacetylation have already been approved by the FDA for the treatment of hematologic malignancies. However, drugs that target the other mechanisms still need to be developed. Recently, 3-deazaneplanocin A (DZNep) was reported to selectively inhibit the trimethylation of lysine 27 on histone H3 (H3K27me3) and lysine 20 on histone H4 (H4K20me3) as well as re-activate silenced genes in cancer cells. This finding opens the door to pharmacological inhibition of histone methylation and we therefore wanted to further study the mechanism of action of 3-deazaneplanocin A in cancer cells. Western blot analysis showed that two other drugs, sinefungin and adenosine-dialdehyde (Adox), have similar effects on the trimethylation H3K27 as 3-deazaneplanocin A and that DZNep is not selective, but globally inhibits histone methylation. Intriguingly, chromatin immunoprecipitation of various histone modifications and microarray analysis show DZNep acts via a different pathway to 5-aza-2-deoxycytidine (5-azaCdR), a DNA methyltransferase inhibitor and gives us an interesting insight into how chromatin structure effects gene expression. We also determine the kinetics of gene activation in order to understand if the induced changes were somatically heritable. We have found that upon removal of DZNep, gene expression is reduced to its original state suggesting that there is a homeostatic mechanism which returns the histone modifications to their ground state after DZNep treatment. Not only do these studies show the strong need for further development of histone methylation inhibitors but also allow us to better understand how chromatin structure affects gene expression.
DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation.
No sample metadata fields
View Samples