Global mammary luminal cells gene expression data from C451A-ERα and WT female mice treated by E2 or E2+Pg during 21 days.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE142297 | GEO | 2019/12/19
REPOSITORIES: GEO
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Project description:Global mammary luminal cells gene expression data from C451A-ERα and WT female mice treated by E2 or E2+Pg during 21 days.
| PRJNA596527 | ENA
Project description:Background: Estrogen receptor (ERα) and aryl hydrocarbon receptor (AHR) are two nuclear receptors involved in regulating gene expression. ERα and AHR are regulated by estradiol(E2) and TCDD respectively. They are also regulated by dietary ligands including 3,3´diindolylmethane (DIM) and resveratrol (RES). DIM is an ERα and AHR agonist, while RES is an ERα agonist and AHR antagonist. Few studies have investigated the impact of RES and DIM on ERα and AHR signaling at a genome-wide level. This study assessed ERα and AHR binding and associated gene expression changes after treatment of MCF-7 human breast cancer cells with DIM, RES, E2, TCDD, and E2+TCDD for 1 hour and 6 hours before ChIP and RNA sequencing respectively. Results: 88% and 86% of the ERα bound sites after RES and DIM overlapped with E2 ERα sites. RES and DIM resulted in 577 and 446 differentially expressed genes (DEGs) respectively compared to 866 after E2. 68% and 62.3% of the DEGs after RES and DIM were closest to an ERα binding site. Motif analysis indicated enrichment for AHRE motif among DIM ERα sites but not among E2 or RES ERα sites. Both DIM and E2+TCDD resulted in greater genome wide binding of AHR than TCDD. DIM and E2+TCDD resulted in 10546 and 8904 AHR and ERα co-occupied sites respectively. While co-occupied sites for both enriched for the AHR and ERE motif among others, DIM mediated co-occupied sites enriched for Tcfcp2l1, Tgif1, Gata3 motifs while E2+TCDD mediated ones enriched for the NF1 and Ppara motifs. Overlap of coregulated DEGs after DIM and E2+TCDD indicated 123 were the same among both with 81 and 85 unique coregulated DEGs respectively. Enrichment analysis indicated that more enrichment terms were different than similar for coregulated genes after E2+TCDD and DIM. Conclusions: AHR activation is responsible for DIM mediated reduced regulation of gene expression by ERα relative to E2 and only a subset of the DEG’s after DIM and RES are ERα targets indicating future studies into other transcription factors regulated by DIM and RES are needed for insights into the regulation of gene expression by these ligands.
2023-10-16 | GSE232234 | GEO
Project description:To examine the effects of ERα antagonism (giredestrant) on Esr1-wildtype and Esr1-mutant mammary glands, animals were treated with hormone pellets (E2, P4), then dosed daily with vehicle (MCT) or giredestrant (30 mg/kg, p.o.) for four days. Following dosing, individual mammary epithelial cell populations were FACS-isolated and sequenced.
2024-10-31 | GSE205576 | GEO
Project description:To examine the effects of ERα antagonism (giredestrant) on Esr1-wildtype and Esr1-mutant mammary glands, animals were treated with hormone pellets (E2, P4), then dosed daily with vehicle (MCT) or giredestrant (30 mg/kg, p.o.) for four days. Following dosing, individual mammary epithelial cell populations were FACS-isolated and sequenced.
2024-10-31 | GSE205575 | GEO
Project description:To examine the effects of ERα antagonism (giredestrant) on Esr1-wildtype and Esr1-mutant mammary glands, animals were treated with hormone pellets (E2, P4), then dosed daily with vehicle (MCT) or giredestrant (30 mg/kg, p.o.) for four days. Following dosing, EpCAM+ cells were isolated and used for single cell sequencing. For each condition, cells from 2 animals were pooled for sequencing.
2024-10-31 | GSE205573 | GEO
Project description:To examine the effects of ERα antagonism (giredestrant) on Esr1-wildtype and Esr1-mutant mammary glands, animals were treated with hormone pellets (E2, P4), then dosed daily with vehicle (MCT) or giredestrant (30 mg/kg, p.o.) for four days. Following dosing, individual mammary epithelial cell populations were FACS-isolated and sequenced. Rare giredestrant-induced novel cells (at least 1000 cells per sample) were collected from WT tissues and compared to mutant-induced novel cells.
2024-10-31 | GSE205577 | GEO
Project description:To advance understanding of mechanisms leading to biological and transcriptional endpoints related to estrogen action in the mouse uterus, we have mapped ERα and RNA polymerase II binding sites using chromatin immunoprecipitation (ChIP) followed by sequencing of enriched chromatin fragments (ChIP-seq). In the absence of hormone, 5184 ERα binding sites were apparent in the vehicle treated ovariectomized uterine chromatin, while 17240 were seen one hour after estrogen (E2) treatment, indicating that some sites are occupied by unliganded ERα, and that ERα binding is increased by E2. Approximately 15% of the uterine ERα binding sites were adjacent to (<10 KB) annotated transcription start sites and many sites are found within genes or are found more than 100 KB distal from mapped genes; however, the density (sites per bp) of ERα binding sites is significantly greater adjacent to promoters. An increase in quantity of sites but no significant positional differences were seen between vehicle and E2 treated samples in the overall locations of ERα binding sites either distal from, adjacent to or within genes. Analysis of the PolII data revealed the presence of poised promoter proximal PolII on some highly upregulated genes. Additionally, co-recruitment of PolII and ERα to some distal enhancer regions was observed. A de novo motif analysis of sequences in the ERα bound chromatin confirmed that estrogen response elements (EREs) were significantly enriched. Interestingly, in areas of ERα binding without predicted ERE motifs, homeodomain transcription factor (Hox) binding motifs were significantly enriched. The integration of the ERα and PolII binding sites from our uterine ChIP-seq data with transcriptional responses revealed in our uterine microarrays has the potential to greatly enhance our understanding of mechanisms governing estrogen response in uterine and other estrogen target tissues.
2012-04-09 | GSE36455 | GEO
Project description:The White Adipose Tissue (WAT) has a major influence on energy metabolic functions and expresses the estrogen receptor ERα. Ovariectomized mice or mice carrying an ERα knock-out gene (ERKO), have a higher risk of becoming obese and developing metabolic disorders such as diabetes or dyslipidemia. To identify the direct target genes of ERα in visceral WAT, we treated ovariectomized mice with estradiol (E2) for 2 hours and proceeded to a genome-wide analysis of ERα binding sites to systemically identify them. We demonstrate that the E2/ERα pathway increases the expression of genes involved in the balance between lipids and glucose catabolism, the energy expenditure through the TCA cycle and the respiratory membrane chain. ERα binding sites and gene expression analysis in visceral and subcutaneous WAT, brown adipose tissue and liver show a specific program for each tissue. Our results are consistent with E2/ERα signaling protecting against metabolic diseases such as obesity by regulating an important gene regulatory network that helps maintaining normal metabolic functions in WAT.
2024-12-31 | GSE121691 | GEO
Project description:Estrogen receptor alpha (ERα)-positive breast cancers, while initially being responsive, eventually develop resistance to ERα targeted therapies through ERα-dependent and ERα-independent mechanisms. Through functional genomic studies we report heretofore unrecognized role for the axon guidance dependence receptor UNC5A in fine-tuning estradiol (E2) and anti-estrogen response. Knockdown of the estradiol-inducible UNC5A caused unrestricted ERα signaling as evident from deregulated E2-regulated gene expression and E2-independent tumorigenesis accompanied with multi-organ metastatic spread in xenograft models. UNC5A-knockdown cells displayed luminal/basal hybrid phenotype characterized by elevated expression of basal/stem cell enriched ∆Np63 and ITGA6 (CD49f), anti-apoptotic BCL2, and the lymphangiogenic factor NTN4 but lower expression of luminal/alveolar differentiation-associated factor ELF5 while maintaining functional ERα. Thus, UNC5A is a new regulator of ERα with a tumor/metastasis suppressive activity. Significance: ERα signaling network plays a significant role in ~70% of breast cancers. While the signaling molecules that partner with ERα to augment E2-dependent signaling and promote breast cancer progression have been well studied, negative feedback proteins that attenuate ERα signaling and their contribution to breast cancer progression are yet to be identified. This study reports E2-inducible UNC5A as a critical attenuator of ERα signaling and its reduced expression in primary breast cancer is associated with poor outcome. UNC5A potentially controls ERα signaling by restricting PI3K/AKT:ERα crosstalk needed for E2-independent activity while simultaneously maintaining ERα-dependent luminal differentiation program. These findings have important implications in developing strategies to combat anti-estrogen resistance and to improve clinical utility of PI3K/AKT inhibitors.
2018-11-22 | GSE89700 | GEO