Non-linear relationship between chromatin accessibility and estradiol-regulated gene expression
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ABSTRACT:
PROVIDER: PRJNA604072 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10992900_1.fastq.gz | Fastqsanger.gz | |||
| SRR10992900_2.fastq.gz | Fastqsanger.gz | |||
| SRR10992901_1.fastq.gz | Fastqsanger.gz | |||
| SRR10992901_2.fastq.gz | Fastqsanger.gz | |||
| SRR10992902_1.fastq.gz | Fastqsanger.gz |
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Project description:Chromatin accessibility is central to basal and inducible gene expression. Through ATAC-seq experiments in Estrogen Receptor-positive (ER+) breast cancer cell line MCF-7 and integrationvwith multi-omics data, we found that estradiol (E2) induced chromatin accessibility changes in the widely studied E2-regulated genes. As expected, open chromatin regions associated with E2-inducible gene expression showed enrichment of estrogen response element and those associated with E2-repressible gene expression were enriched for PBX1, PBX3, and ERE. Surprisingly, a significant number of E2-inducible genes displayed closed promoters/enhancers and these were enriched for binding for transcription factors such as NF-Y, FOXA1, GRHL2, and BATF, which are known to interact with nucleosomes. While a significant number of open chromatin regions showed FOXA1 occupancy in the absence of E2, E2-treatment further enhanced FOXA1 occupancy suggesting that ER-E2 enhances chromatin occupancy of FOXA1 to a subset of E2-regulated genes. In summation, our results reveal complex mechanisms of ER-E2 interaction with nucleosomes.
2020-01-31 | GSE144580 | GEO
Project description:The fission yeast Schizosaccharomyces pombe lacks a diverse toolkit of inducible promoters for experimental manipulation. Available inducible promoters suffer from slow induction kinetics, limited control of expression levels and/or a requirement for defined growth medium. In particular, no S. pombe inducible promoter systems exhibit a linear dose response, which would allow expression to be tuned to specific levels. We have adapted a fast, orthogonal promoter system with a large dynamic range and a linear dose response, based on _-estradiol-regulated function of the human estrogen receptor, for use in S. pombe. We show that this promoter system, termed Z3EV, turns on quickly, can reach a maximal induction of 20 fold, and exhibits a linear dose response over its entire induction range, with few off target effects. We demonstrate the utility of this system by regulating the mitotic inhibitor Wee1 to create a strain in which cell size is regulated by _-estradiol concentration. This promoter system will be of great utility for experimentally regulating gene expression in fission yeast.
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Project description:Scarcity of gender specific donor hearts highlights the importance of mesenchymal stem cells (MSCs) as a therapeutic tool for heart repair. However, inefficient incorporation, retention, and activity of MSCs in cardiac tissue remains an obstacle. Since surge in follicular estradiol (μmolar-range) triggers tissue remodeling (e.g. ovulation) and estradiol exerts beneficial actions on the cardiovascular system, we hypothesized that estradiol may promote/improve MSC-mediated cardiac repair processes. Methods: Wharton’s jelly-derived MSCs were used, to assess the effects of estradiol on their proliferation, directed-migration and engraftment in murine heart slices, ex vivo. Results: MSCs expressed estrogen receptors (ERs) α and β, and estradiol promoted MSC proliferation (measured using xCELLigence real-time cell-impedance system and DNA-quantification). Estradiol up-regulated mRNA (qRT-PCR) and protein expression (western blotting) of ERα, ERβ, EMMPRIN, and MMP-9, yet down-regulated MMP-2 expression. In MSCs estradiol, up-regulated mRNA expression of VEGF-A, VCAM-1, and angiogenin, and stimulated NO production via ER. Proteomic analysis revealed that in MSCs estradiol up-regulated 47 proteins, down-regulated 7 proteins, and increased the expression of key biochemical components/pathways involved in tissue repair. In MSCs co-cultured with murine heart-slices, estradiol significantly induced MSC migration in an ER-dependent fashion (and preferentially via ERα) and significantly increased the secretion of MMP-2, MMP-9, angiogenin and VEGF. Conclusion: Estradiol facilitates the integration/engraftment of MSCs into heart slices by promoting MSC proliferation and migration and these beneficial effects are mediated via increases in molecules/pathways involved in tissue remodeling and angiogenesis. Priming of MSCs with estradiol may enhance their ability to repair/regenerate cardiac tissue in women.
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Project description:Endometrioid endometrial carcinoma (EEC), an estradiol-related disease, remains a serious health threat to women because of its high incidence and trend of rejuvenation. Accumulating evidence has highlighted that microRNAs (miRNAs) and messenger RNAs (mRNAs) play important roles in various biological processes involved in the pathogenesis of EEC. This study aimed to identify the potential prognostic biomarkers associated with EEC regulated by estradiol.
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Project description:Endometrioid endometrial carcinoma (EEC), an estradiol-related disease, remains a serious health threat to women because of its high incidence and trend of rejuvenation. Accumulating evidence has highlighted that microRNAs (miRNAs) and messenger RNAs (mRNAs) play important roles in various biological processes involved in the pathogenesis of EEC. This study aimed to identify the potential prognostic biomarkers associated with EEC regulated by estradiol.
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Project description:Objective: To examine the effect of estradiol on gene expression in the monkey iliac arteries. Design: Eight ovariectomized cynomolgus monkeys were on a high fat diet for 6.5 years. The left iliac artery was biopsied before randomization to estradiol (1 mg Estrace® per day, n=4) or vehicle (n=4) for 8 months. The right iliac artery was obtained at necropsy. Gene expression in the iliac arteries in response to estradiol was determined by DNA microarray and confirmed by real time RT-PCR. Results: Atherosclerotic lesions in the iliac arteries ranged in size from 0-0.61 mm2 in estrogen-treated animals and from of 0-0.873 mm2 in controls. 106 genes were shown to be down-regulated and 26 genes were up-regulated in the monkey iliac arteries in response to estradiol. Among the genes shown to be up-regulated by DNA microarray and confirmed by real time RT-PCR were components of the insulin-like growth factor (IGF) pathway, IGF-1, IGF binding protein 4 (IGFBP4) and IGFBP5. Components of the Wnt signaling pathway were also up-regulated, including secreted frizzled-related protein 2 (SFRP2), SFRP4, low density lipoprotein receptor-related protein 6 (LRP6), and Wnt 1 inducible signaling pathway protein 2 (WISP2). Conclusions: The modest effect of estradiol on gene expression in monkey iliac arteries reported herein may reflect a reduction in response to estradiol as a result of the effect of the altered environment of the artery containing atherosclerotic plaque.
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Project description:The HPV16-E7 oncoprotein and 17β-estradiol are import factors for the induction of premalignant lesions and cervical cancer. The study of these factors is crucial for a better understanding of cervical tumorigenesis. In this study, we performed a microarray analysis to obtain a global gene expression profile induced by both, HPV16-E7 and 17β-estradiol in cervical tissue of K14E7 transgenic mice. We found that 17β-estradiol is the main cause of the up-regulation of a large number of cellular genes involved in the immune response whereas E7 oncoprotein mainly affects the cellular metabolism. Our microarray data also shows some novel differentially expressed genes that were not previously reported in cervical cancer. The identification of these genes, regulated by E7 and 17β-estradiol, provides the basis for further studies on their role in cervical carcinogenesis. 15 Mouse Gene 1.0 ST Affymetrix microarrays were used to analyze gene expression of cervical tissue from K14E7 hemizygote and nontransgenic FvB control virgin female untreated and treated mice. Briefly, one-month virgin female transgenic and nontransgenic mice were implanted in the dorsal skin with continuous release pellets delivering 0.05 mg of17-β estradiol over 60 days. As control samples we used K14E7 and FvB untreated mice. For the microarray analysis we used triplicates for each group (3 treated K14E7 mice, 3 treated FvB mice, 3 untreated K14E7 mice, 3 untreated FvB mice).
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