Estrogen signaling and epigenetic modifications, in particular DNA methylation, are involved in regulation of gene expression in breast cancers. Here we investigated a potential regulatory cross-talk between these two pathways by identifying their common target genes and exploring potential underlying molecular mechanisms in human MCF7 breast cancer cells. Principal Findings: Gene expression profiling revealed that the expression of approximately 150 genes was influenced by both 17-estradiol (E2) and a hypomethylating agent 5-aza-2-deoxycytidine (DAC). Based on gene ontology (GO), CpG island prediction analysis and previously reported estrogen receptor (ER) binding regions, we selected six genes for further analysis (BTG3, FHL2, PMAIP1, BTG2, CDKN1A and TGFB2). GO analysis suggests that these genes are involved in intracellular signaling cascades, regulation of cell proliferation and apoptosis, while CpG island prediction of promoter regions reveals that the promoters of these genes contain at least one CpG island. Using chromatin immunoprecipitation, we show that ER is recruited to CpG islands in promoters, but neither in an E2- nor in a DAC-dependent fashion. DAC treatment reactivates the expression of all selected genes although only the promoters of BTG3 and FHL2 genes are methylated, with E2 treatment showing no effect on the methylation status of these promoters. Conclusions: We identified a set of genes regulated by both estrogen signaling and DNA methylation. However, our data does not support a direct molecular interplay of mediators of estrogen and epigenetic signaling at promoters of regulated genes.
Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The transcriptional coregulator MAML1 affects DNA methylation and gene expression patterns in human embryonic kidney cells.
Cell line, Treatment
View SamplesMastermind-like 1 (MAML1) is a transcriptional coregulator that has been associated with early development of many systems such as neuronal, muscular, cardiovascular and urogenital. The present study aimed to explore the genome-wide effects of MAML1 on gene expression and DNA methylation in human embryonic kidney cells. RNA expression was measured using a microarray that screens approximately 36,000 transcripts, and DNA methylation was determined for 450,000 CpG sites. 225 genes were found to be differentially expressed, while 11802 CpG sites were found to be differentially methylated in MAML1-expressing cells. A subset of 211 differentially methylated loci was associated with the expression of 85 genes. Gene ontology analysis revealed that these genes are involved in the regulation of urogenital system development, cell adhesion and embryogenesis.
The transcriptional coregulator MAML1 affects DNA methylation and gene expression patterns in human embryonic kidney cells.
Cell line, Treatment
View SamplesThe Nanos family of RNA-binding proteins has been implicated in the specification of primordial germ cells (PGCs) in a wide range of metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of PGCs lacking the nanos homologues nos-1 and nos-2 in C. elegans using cell sorting and RNA-seq. nos-1nos-2 PGCs fail to silence hundreds of genes normally expressed in oocytes and somatic cells, a phenotype reminiscent of PGCs lacking the repressive PRC2 complex. The nos-1nos-2 phenotype depends on LIN-15B, a broadly expressed synMuvB class transcription factor known to antagonize PRC2 activity in somatic cells. LIN-15B is maternally-inherited by all embryonic cells and is down-regulated specifically in PGCs in a nos-1nos-2-dependent manner. Consistent with LIN-15B being a critical target of Nanos regulation, inactivation of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These studies demonstrate a central role for Nanos in reprogramming the transcriptome of primordial germ cells away from an oocyte/somatic fate by down-regulating an antagonist of PRC2 activity. Overall design: 30 RNA-seq samples are inclued in this study. These include PGC transcriptomes from wild-type, nos-1(gv5)nos-2(RNAi), mes-2(RNAi), mes-4(RNAi), nos-1(gv5)nos-2(RNAi);lin15-B(RNAi) and biological replicates.
Recruitment of mRNAs to P granules by condensation with intrinsically-disordered proteins.
Subject
View SamplesSignificant recent progress has been made with understanding eosinophilic gastrointestinal disorders (EGIDs) yet most studies have focused on eosinophilic esophagitis (EoE). Herein, we aimed to provide fundamental information about the molecular characteristics of eosinophilic gastritis (EG).
Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome.
Specimen part, Disease, Disease stage
View Samples3 eosinophilic esophagitis biopsies, cultured and stimulated with IL-13 : each of them was either left unstimulated or stimulated (100ng for 48h)
IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids.
No sample metadata fields
View SamplesThe Staphylococcus aureus two-component regulatory system, SrrAB, coordinates hypoxic responses during in vitro growth conditions.
Bacterial Hypoxic Responses Revealed as Critical Determinants of the Host-Pathogen Outcome by TnSeq Analysis of Staphylococcus aureus Invasive Infection.
No sample metadata fields
View SamplesThis study was aimed at understanding the genome-wide binding and regulatory role of the DAXX transcriptional repressor, recently implicated in PCa. ChIP-Seq analysis of genome-wide distribution of DAXX in PC3 cells revealed over 59,000 DAXX binding sites, found at regulatory enhancers and promoters. ChIP-Seq analysis of DNA methyltransferase 1 (DNMT1), which is a key epigenetic partner for DAXX repression, revealed that DNMT1 binding was restricted to a small number of DAXX sites. DNMT1 and DAXX bound close to transcriptional activator motifs. DNMT1 sites were found to be dependent on DAXX for recruitment by analyzing DNMT1 ChIP-Seq following DAXX knockdown (K/D), corroborating previous findings that DAXX recruits DNMT1 to repress its target genes. Massively parallel RNA sequencing (RNA-Seq) was used to compare the transcriptomes of WT and DAXX K/D PC3 cells. Genes induced by DAXX K/D included those involved in autophagy, and DAXX ChIP-Seq peaks were found close to the transcription start sites (TSS) of autophagy genes, implying they are more likely to be regulated by DAXX. Overall design: Determine changes in gene expression levels between WT and DAXX K/D prostate cancer cells by RNA-Seq (PC3 Cells).
The DAXX co-repressor is directly recruited to active regulatory elements genome-wide to regulate autophagy programs in a model of human prostate cancer.
No sample metadata fields
View SamplesIn order to confirm the role of fatty acid -oxidation in Src regulation, we performed gene expression analysis in MDA231 cells from in vivo model treated with ETX or knockdown of CPT1 or CPT2 using shRNA. As expected, inhibition of -oxidation showed a gene expression pattern that is opposite to the published Src regulated gene pattern. The known Src up-regulated genes are down-regulated and Src down-regulated genes are up-regulated in -oxidation inhibited cells. Western Blotting further confirmed the gene expression pattern. Knockdown of CPT1 or CPT2 inhibited Src Y416 autophosphorylation as observed with ETX.
Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer.
Cell line
View SamplesWe used a transmitochondrial cybrid (cybrids)-based discovery approach to identify mitochondria-regulated cancer pathways in TN BCa. Cybrids were generated under a moderately metastatic TN BCa cell line SUM159 as the common nuclear background with mitochondria from benign breast epithelium (A1N4) and moderately metastatic (SUM159) TN BCa cells. In vitro and in vivo studies suggested that even under the common moderately cancerous nuclear background, mitochondria from benign cells inhibit and metastatic cell induce cancer properties of a moderately aggressive TN BCa cell. Gene expression studies identified c-Src onco-pathway as one of the major cancer pathways altered according to the mitochondria status of the cybrids.
Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer.
Specimen part
View Samples