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Project description:Endometrial estrogen receptor-α (ESR1) is indispensable for epithelial and stromal proliferation and differentiation during decidualization, yet the gene targets of estradiol (E2) / ESR1 in human stromal cells and associated mechanisms remain unknown. In this study, we characterized global E2-ESR1‒dependent transcriptomic changes and ESR1 recruitment to chromatin. Human endometrial stromal cells were isolated from 4 premenopausal women for primary cell culture. Genome-wide RNA expression by RNA-sequencing was compared in endometrial stromal cells with or without siRNA knockdown of ESR1 in the presence or absence of E2 (n=2). Genome-wide recruitment of ESR1 to chromatin was assessed by chromatin immunoprecipitation sequencing using an antibody against ESR1 was performed to examine binding to target genes (n=1).
2020-07-06 | GSE151392 | GEO
Project description:Endometrial estrogen receptor-α (ESR1) is indispensable for epithelial and stromal proliferation and differentiation during decidualization, yet the gene targets of estradiol (E2) / ESR1 in human stromal cells and associated mechanisms remain unknown. In this study, we characterized global E2-ESR1‒dependent transcriptomic changes and ESR1 recruitment to chromatin. Human endometrial stromal cells were isolated from 4 premenopausal women for primary cell culture. Genome-wide RNA expression by RNA-sequencing was compared in endometrial stromal cells with or without siRNA knockdown of ESR1 in the presence or absence of E2 (n=2). Genome-wide recruitment of ESR1 to chromatin was assessed by chromatin immunoprecipitation sequencing using an antibody against ESR1 was performed to examine binding to target genes (n=1).
2020-07-06 | GSE151393 | GEO
Project description:Genome-wide estrogen receptor-α binding and action in human endometrial stromal cells
| PRJNA635668 | ENA
Project description:Genome-wide estrogen receptor-α binding and action in human endometrial stromal cells [ChIP-Seq]
| PRJNA635667 | ENA
Project description:Genome-wide estrogen receptor-α binding and action in human endometrial stromal cells [RNA-Seq]
| PRJNA635669 | ENA
Project description:Estrogen regulates several biological processes through estrogen receptor alpha (ERalpha) and ERbeta. ERalpha-estrogen signaling is additionally controlled by extracellular signal activated kinases such as AKT. In this study, we analyzed the effect of AKT on genome-wide ERalpha binding in MCF-7 breast cancer cells. Parental and AKT-overexpressing cells displayed 4,349 and 4,359 ERalpha binding sites, respectively, with approximately 60% overlap. In both cell types, approximately 40% of estrogen-regulated genes associate with ERalpha binding sites; a similar percentage of estrogen-regulated genes are differentially expressed in two cell types. Based on pathway analysis, these differentially estrogen-regulated genes are linked to transforming growth factor beta (TGF-beta), NF-kappaB, and E2F pathways. Consistent with this, the two cell types responded differently to TGF-beta treatment: parental cells, but not AKT-overexpressing cells, required estrogen to overcome growth inhibition. Combining the ERalpha DNA-binding pattern with gene expression data from primary tumors revealed specific effects of AKT on ERalpha binding and estrogen-regulated expression of genes that define prognostic subgroups and tamoxifen sensitivity of ERalpha-positive breast cancer. These results suggest a unique role of AKT in modulating estrogen signaling in ERalpha-positive breast cancers and highlights how extracellular signal activated kinases can change the landscape of transcription factor binding to the genome.
| S-EPMC2593438 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-01-07 | E-GEOD-40767 | biostudies-arrayexpress
Project description:BACKGROUND:The forkhead transcription factor FOXM1 is a key regulator of the cell cycle. It is frequently over-expressed in cancer and is emerging as an important therapeutic target. In breast cancer FOXM1 expression is linked with estrogen receptor (ER?) activity and resistance to endocrine therapies, with high levels correlated with poor prognosis. However, the precise role of FOXM1 in ER positive breast cancer is not yet fully understood. RESULTS:The study utilizes chromatin immunoprecipitation followed by high-throughput sequencing to map FOXM1 binding in both ER?-positive and -negative breast cancer cell lines. The comparison between binding site distributions in the two cell lines uncovered a previously undescribed relationship between binding of FOXM1 and ER?. Further molecular analyses demonstrated that these two factors can bind simultaneously at genomic sites and furthermore that FOXM1 regulates the transcriptional activity of ER? via interaction with the coactivator CARM1. Inhibition of FOXM1 activity using the natural product thiostrepton revealed down-regulation of a set of FOXM1-regulated genes that are correlated with patient outcome in clinical breast cancer samples. CONCLUSIONS:These findings reveal a novel role for FOXM1 in ER? transcriptional activity in breast cancer and uncover a FOXM1-regulated gene signature associated with ER-positive breast cancer patient prognosis.
| S-EPMC3663086 | biostudies-literature
Project description:Estrogen-related receptor alpha (ERRα), which shares structural similarities with estrogen receptors, is associated with tumor progression in endometrial cancer, but little is known about the detailed underlying mechanism. We investigated whether ERRα, in cooperation with peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), could participate in epithelial-mesenchymal transition (EMT) in endometrial cancer through cancer-stromal interactions. Two endometrial cancer cell lines, Ishikawa and HEC-1A, transfected with ERRα/PGC-1α expression plasmids or silenced for ERRα expression, were co-cultured with telomerase-transformed human endometrial stromal cells (T-HESCs). We found that EMT-associated factors including vimentin, Snail, and zinc finger E-box binding homeobox 1 were upregulated in cancer cells overexpressing ERRα/PGC-1α and that transforming growth factor-beta (TGF-β) was induced in T-HESCs in the same conditions. In contrast, ERRα knockdown suppressed EMT-associated factors in cancer cells and TGF-β in T-HESCs. ERRα/PGC-1α overexpression increased the expression of EMT-associated factors after TGF-β exposure; however, it decreased E-cadherin at protein level. ERRα knockdown suppressed EMT-associated factors in the presence of TGF-β, whereas E-cadherin remained unchanged. Matrigel invasion assays revealed that ERRα knockdown attenuated the stimulation of migration and invasion by TGF-β. These findings suggest that ERRα is a potential target for inhibiting TGF-β-induced EMT through cancer-stromal interactions in endometrial cancer.
| S-EPMC6491648 | biostudies-literature
Project description:Using a chromatin immunoprecipitation-paired end diTag cloning and sequencing strategy, we mapped estrogen receptor alpha (ERalpha) binding sites in MCF-7 breast cancer cells. We identified 1,234 high confidence binding clusters of which 94% are projected to be bona fide ERalpha binding regions. Only 5% of the mapped estrogen receptor binding sites are located within 5 kb upstream of the transcriptional start sites of adjacent genes, regions containing the proximal promoters, whereas vast majority of the sites are mapped to intronic or distal locations (>5 kb from 5' and 3' ends of adjacent transcript), suggesting transcriptional regulatory mechanisms over significant physical distances. Of all the identified sites, 71% harbored putative full estrogen response elements (EREs), 25% bore ERE half sites, and only 4% had no recognizable ERE sequences. Genes in the vicinity of ERalpha binding sites were enriched for regulation by estradiol in MCF-7 cells, and their expression profiles in patient samples segregate ERalpha-positive from ERalpha-negative breast tumors. The expression dynamics of the genes adjacent to ERalpha binding sites suggest a direct induction of gene expression through binding to ERE-like sequences, whereas transcriptional repression by ERalpha appears to be through indirect mechanisms. Our analysis also indicates a number of candidate transcription factor binding sites adjacent to occupied EREs at frequencies much greater than by chance, including the previously reported FOXA1 sites, and demonstrate the potential involvement of one such putative adjacent factor, Sp1, in the global regulation of ERalpha target genes. Unexpectedly, we found that only 22%-24% of the bona fide human ERalpha binding sites were overlapping conserved regions in whole genome vertebrate alignments, which suggest limited conservation of functional binding sites. Taken together, this genome-scale analysis suggests complex but definable rules governing ERalpha binding and gene regulation.
| S-EPMC1885282 | biostudies-literature