Estrogen receptor alpha (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells. Overall design: RNA-seq was used to study the effects of the D538G mutation on gene expression
Estrogen-independent molecular actions of mutant estrogen receptor 1 in endometrial cancer.
Cell line, Treatment, Subject, Time
View SamplesWe report the transcriptome changes that result of the genomic deletion of one or two alleles of an islet-specific long non-coding RNA (Blinc1) in isolated pancreas from e15.5 mouse embryos. Overall design: Pancreas from e15.5 embryos were dissected and total RNA extracted. Libraries were prepared from total RNA (RIN>8) with the TruSeq RNA prep kit (Illumina) and sequenced using the HiSeq2000 (Illumina) instrument. More than 20 million reads were mapped to the mouse genome (UCSC/mm9) using Tophat (version 2.0.4) with 4 mismatches and 10 maximum multiple hits. Significantly differentially expressed genes were calculated using DEseq.
βlinc1 encodes a long noncoding RNA that regulates islet β-cell formation and function.
Specimen part, Subject
View SamplesThe Snf1 kinase plays a critical role in recalibrating cellular metabolism in response to glucose depletion. Hundreds of genes show changes in expression levels when the SNF1 gene is deleted. However, cells can adapt to the absence of a specific gene when grown in long term culture. Here we apply a chemical genetic method to rapidly and selectively inactivate a modified Snf1 kinase using a pyrazolopyrimidine inhibitor. By allowing cells to adjust to a change in carbon source prior to inhibition of the Snf1 kinase activity, we identified a set of genes whose expression increased when Snf1 was inhibited. Prominent in this set are genes that are activated by Gcn4, a transcriptional activator of amino acid biosynthetic genes. Deletion of Snf1 increased Gcn4 protein levels without affecting its mRNA levels. The increased Gcn4 protein levels required the Gcn2 kinase and Gcn20, regulators of GCN4 translation. These data indicate that Snf1 functions upstream of Gcn20 to regulate control of GCN4 translation.
A chemical genomics study identifies Snf1 as a repressor of GCN4 translation.
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Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.
Specimen part
View SamplesTo investgate the role of EBF1 in human adipocyte, we performed global expression profiling in human adipocytes transfected with siRNA targeting EBF1.
Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.
Specimen part
View SamplesIllumina expression microarray analysis of shRNA-mediated PRAME knock down TCam-2 cells with and without all trans retinoic acid (ATRA) treatment for 8 days, of TCam-2 cells with and without ATRA (8d) and of in vitro cultivated GCC cell lines TCam-2, 2102EP, NCCIT and JAR. These data are part of the article 'The Cancer / Testis-Antigen PRAME supports the pluripotency network and represses somatic and germ cell differentiation programs in seminomas'.
The cancer/testis-antigen PRAME supports the pluripotency network and represses somatic and germ cell differentiation programs in seminomas.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
Sex, Age, Specimen part, Subject
View SamplesWe used an unbiased systems biology approach to study the regulation of gene expression in human adipose tissue focusing on inflammation. We show that microRNAs play a major role as regulators of CCL2 production in obesity.
Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
Age, Specimen part
View SamplesWe used an unbiased systems biology approach to study the regulation of gene expression in human adipose tissue focusing on inflammation. We show that microRNAs play a major role as regulators of CCL2 production in obesity.
Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
Sex, Age, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MLL2, Not MLL1, Plays a Major Role in Sustaining MLL-Rearranged Acute Myeloid Leukemia.
Specimen part, Treatment
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