To explore the global mechanisms of estrogen-regulated transcription, we used chromatin immunoprecipitation coupled with DNA microarrays to determine the localization of RNA polymerase II (Pol II), estrogen receptor alpha (ERalpha), steroid receptor coactivator proteins (SRC), and acetylated histones H3/H4 (AcH) at estrogen-regulated promoters in MCF-7 cells with or without estradiol (E2) treatment. In addition, we correlated factor occupancy with gene expression and the presence of transcription factor binding elements. Using this integrative approach, we defined a set of 58 direct E2 target genes based on E2-regulated Pol II occupancy and classified their promoters based on factor binding, histone modification, and transcriptional output. Many of these direct E2 target genes exhibit interesting modes of regulation and biological activities, some of which may be relevant to the onset and proliferation of breast cancers. Our studies indicate that about one-third of these direct E2 target genes contain promoter-proximal ERalpha-binding sites, which is considerably more than previous estimates. Some of these genes represent possible novel targets for regulation through the ERalpha/AP-1 tethering pathway. Our studies have also revealed several previously uncharacterized global features of E2-regulated gene expression, including strong positive correlations between Pol II occupancy and AcH levels, as well as between the E2-dependent recruitment of ERalpha and SRC at the promoters of E2-stimulated genes. Furthermore, our studies have revealed new mechanistic insights into E2-regulated gene expression, including the absence of SRC binding at E2-repressed genes and the presence of constitutively bound, promoter-proximally paused Pol IIs at some E2-regulated promoters. These mechanistic insights are likely to be relevant for understanding gene regulation by a wide variety of nuclear receptors.
Genomic analyses of transcription factor binding, histone acetylation, and gene expression reveal mechanistically distinct classes of estrogen-regulated promoters.
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View SamplesIncreasing evidence provide support that the mammalian liver contains stem/progenitor cells, but their molecular phenotype, embryological derivation, cell biology as well as of their role in the liver cell turnover and regeneration remain to be further clarified.
Isolation and characterization of a murine resident liver stem cell.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Autoregulation of Th1-mediated inflammation by twist1.
No sample metadata fields
View SamplesGene expression profiling of repeatedly activated compared to recently activated Th1 cells to identify genes that play a role in chronic inflammatory disorders and may qualify as diagnostic or therapeutic targets;
Autoregulation of Th1-mediated inflammation by twist1.
No sample metadata fields
View SamplesThe basic helix-loop-helix transcriptional repressor twist1, as an antagonist of nuclear factor B (NF-B)-dependent cytokine expression, is involved in the regulation of inflammation-induced immunopathology. We could show that twist1 is expressed by activated T helper (Th) 1 effector memory cells. Induction of twist1 in Th cells is dependent on NF-B, nuclear factor of activated T cells (NFAT), and interleukin (IL)-12 signaling via signal transducer and activator of transcription (STAT) 4. Expression of twist1 is transient following T-cell receptor engagement, and increases upon repeated stimulation of Th1 cells. Imprinting for enhanced twist1 expression is characteristic of repeatedly restimulated effector memory Th cells and thus of the pathogenic memory Th cells of chronic inflammation. Th lymphocytes from the inflamed joint or gut tissue of patients with rheumatic diseases, Crohns disease or ulcerative colitis express high levels of twist1. Expression of twist1 in Th1 lymphocytes limits the expression of the cytokines interferon-, IL-2 and tumor necrosis factor-, and ameliorates Th1-mediated immunopathology in delayed-type hypersensitivity and antigen-induced arthritis. In order to identify the effect of twist1 expression on the function of Th cells, twist1 was ectopically expressed and the transcriptome was compared to empty-virus infected control cells. In addition, this experiment allows for the identification of genes regulated by the transcription factor twist1.
Autoregulation of Th1-mediated inflammation by twist1.
No sample metadata fields
View SamplesLeaf transcriptome comparison of untransformed Col-0 Arabidopsis plants with plants transformed to be anti-sense for AtAOX1a (alternative oxidase). Two bio-replicates were sampled, for a total of four microarray chipsCol-0 and anti-sense leaf tissue from a first planting (samples GSM45208 and GSM45231, respectively), and from a second planting made one week later (samples GSM45209 and GSM45278, respectively). See sample descriptions for growth conditions and microarray procedure.
Characterization of transformed Arabidopsis with altered alternative oxidase levels and analysis of effects on reactive oxygen species in tissue.
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View SamplesMurine healthy tissue samples, DCIS and invasive mammary tumors were analyzed in order to identify marker genes which show enhanced expresssion in DCIS and invasive ductal carcinomas.
Identification of early molecular markers for breast cancer.
Specimen part
View SamplesHuman healthy tissue samples, DCIS and invasive mammary tumors were analyzed in order to identify marker genes which show enhanced expresssion in DCIS and invasive ductal carcinomas.
Identification of early molecular markers for breast cancer.
Specimen part, Disease, Disease stage
View SamplesDifferencies between groups between pre and post haematopoietic stem cell transplantation children
Genetic Background of Immune Complications after Allogeneic Hematopoietic Stem Cell Transplantation in Children.
Specimen part, Disease stage
View SamplesDifferences between groups of children with obesity and healthy controls.
Looking for new diagnostic tools and biomarkers of hypertension in obese pediatric patients.
Specimen part, Disease
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