Affymetrix Mouse Genome 430 2.0 arrays were used to measure genome-wide gene expression levels. The results show that high-risk human papillomavirus oncogenes E6 and E7 reprogram the cervical cancer microenvironment independently of and synergistically with estrogen, a critical co-factor in cervical cancer development and maintenance.
Human papillomavirus oncogenes reprogram the cervical cancer microenvironment independently of and synergistically with estrogen.
Specimen part, Treatment
View SamplesThe analysis of several mammalian genomes has revealed between 20,000 to 30,000 genes in each genome, a number that may seem hard to reconcile with the large number of cell types and complex functions of these organisms. The solution to this paradox partly lies in the large array of transcripts that each gene can potentially generate through usage of alternative promoters and the variable levels of transcripts that each gene produces in different tissues and cell types. Thus, in order to understand the mechanisms that control diverse patterns of gene expression in mammals, it is necessary to accurately define the active promoters and monitor their cell or tissue-dependent activity. Previous high throughput strategies for assaying tissue-specific gene expression have primarily relied on measurements of steady-state transcript levels by microarrays or tag sequencing. Here, we employ a new experimental strategy to identify and characterize tissue specific promoters by integrating genome-wide maps of RNA polymerase II (Pol II) binding, chromatin modifications and gene expression profiles. We applied this strategy to mouse embryonic stem cells (mES), and adult brain, heart, kidney, and liver. Our results delineated 24,363 Pol II binding sites throughout the genome, 91% of which correspond to 5 end annotation based on known transcripts and cap-analysis of gene expression (CAGE) and can be regarded as promoters. A majority of these experimentally defined promoters are active in all tissues, while only 4,396 can be characterized as tissue-specific using a quantitative measure of Pol II occupancy. In general, Pol II occupancy at these tissue specific promoters is correlated with the presence of active histone modification marks. However, a set of mES- specific promoters display persistent levels of H3K4me3 in non-ES tissues despite undetectable Pol II binding and transcript. Broadly, our results expand the knowledge of tissue-specific mammalian genes and provide a resource for understanding the transcriptional programs in mammalian development and differentiation.
No associated publication
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Sex, Age, Specimen part, Treatment, Subject
View SamplesTarget genes of four signaling pathways (Notch, Fgf, Retinoic Acid [RA] and Wnt) are identified in the posterior presomitic mesoderm of 12 somite stage zebrafish embryos.
No associated publication
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic binding of PAX8-PPARG fusion protein regulates cancer-related pathways and alters the immune landscape of thyroid cancer.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC).
Specimen part, Cell line, Treatment
View SamplesPAX8-PPARG fusion protein (PPFP) results from a t(2;3)(q13;p25) chromosomal translocation, is found in 30% of follicular thyroid carcinomas, and demonstrates oncogenic capacity in transgenic mice. A PPARG ligand, pioglitazone, is highly therapeutic in mice with PPFP thyroid carcinoma. We used our previously characterized transgenic mouse model of PPFP thyroid carcinoma to identify PPFP binding sites in vivo using ChIP-seq, and to identify genes and pathways regulated by PPFP with and without pioglitazone treatment via integration with RNA-seq and Affymetrix microarray data. This submission contains the Affymetrix microarray data. PPFP and pioglitazone regulated genes involved in lipid and fatty acid metabolism, ribosome function, immune processes, cell death and other cancer-related processes. The RNA-seq data yielded similar findings.
Genomic binding of PAX8-PPARG fusion protein regulates cancer-related pathways and alters the immune landscape of thyroid cancer.
Specimen part, Treatment
View SamplesConventional biochemical and molecular techniques identified previously several genes whose expression is regulated by the aryl hydrocarbon receptor (AHR). We sought to map the complete spectrum of AHR-dependent genes in male adult liver using expression arrays to contrast mRNA profiles in Ahr-null mice (Ahr/) with those in mice with wild-type AHR (Ahr+/+). Transcript profiles were determined both in untreated mice and in mice treated 19 h earlier with 1000 g/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Expression of 456 ProbeSets was significantly altered by TCDD in an AHR-dependent manner, including members of the classic AHRE-I gene battery, such as Cyp1a1, Cyp1a2, Cyp1b1, and Nqo1. In the absence of exogenous ligand, AHR status alone affected expression of 392 ProbeSets, suggesting that the AHR has multiple functions in normal physiology. In Ahr/ mice, only 32 ProbeSets exhibited responses to TCDD, indicating that the AHR is required for virtually all transcriptional responses to dioxin exposure in liver. The flavin-containing monooxygenases, Fmo2 and Fmo3, considered previously to be uninducible, were highly induced by TCDD in an AHR-dependent manner. The estrogen receptor alpha as well as two estrogen-receptor-related genes (alpha and gamma) exhibit AHR-dependent expression, thereby extending cross-talk opportunities between the intensively studied AHR and estrogen receptor pathways. p53 binding sites are over-represented in genes down-regulated by TCDD, suggesting that TCDD inhibits p53 transcriptional activity. Overall, our study identifies a wide range of genes that depend on the AHR, either for constitutive expression or for response to TCDD.
No associated publication
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View SamplesDifferentially expressed genes along the paraxial mesoderm of 12 somite stage zebrafish embryos are identified
Spatiotemporal compartmentalization of key physiological processes during muscle precursor differentiation.
Specimen part
View SamplesEnvironmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders.
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Specimen part
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