Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA223389 | ENA |
REPOSITORIES: ENA
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Project description:Estrogen receptor alpha (ERa) has generally been thought to be transcriptionally inactive until it binds estrogen. Here we show that unliganded ERa, far from being transcriptionally inert, regulates a large number of genes both in vascular endothelial cells (ECs) and in mouse aorta. The genes regulated by unliganded ERa in the aorta (largely composed of smooth muscle cells) differ from those in ECs, and aorta- and EC-regulated promoters show enrichment in binding sites for distinct sets of transcription factors. In vitro, the presence of unliganded ERa decreases the migration and proliferation of ECs, and also increases proliferation of SMCs. Consistent with these effects on individual cells in vitro, mice lacking ERa, in the absence of estrogen, show significantly less SMC proliferation and medial thickening after carotid artery wire injury than ER intact mice. The effects of unliganded ERa on vascular gene expression, cell function in vitro and vascular injury responses in vivo are all reversed by the addition of estrogen. Taken together, these results indicate that unliganded ERa regulates vascular gene expression, vascular cell function, and vascular injury responses, and that the cardiovascular protective effects of estrogen may largely be due to the reversal of these effects of unliganded ERa. These results have important implications for the vascular health of men and post-menopausal women with vascular ERa and low circulating levels of estrogen. This study also raises the possibility that the steroid receptor family could have substantial hormone-independent functions in the vasculature and in other tissues.
2016-11-22 | GSE51535 | GEO
Project description:Genome-wide activity of unliganded Estrogen Receptor alpha in breast cancer cells [ChIP-Seq]
| PRJNA232304 | ENA
Project description:Genome-wide activity of unliganded Estrogen Receptor alpha in breast cancer cells [RNA-Seq]
| PRJNA232305 | ENA
Project description:Coativator Function Defines the Active Estrogen Receptor Alpha Cistrome
| PRJNA121689 | ENA
Project description:Estrogen Receptor ? (ER?) has central role in hormone-dependent breast cancer and its ligand-induced functions have been extensively characterized. However, evidence exists that ER? has functions which are independent of ligands. In the present work, we investigated the binding of ER? to chromatin in absence of ligands, and its function(s) on gene regulation. We demonstrated that in MCF7 breast cancer cells unliganded ER? binds to more than four thousands chromatin sites. Unexpectedly, although almost entirely comprised in the larger group of estrogen-induced binding sites, we found that unliganded-ER? binding is specifically linked to genes with developmental functions, as compared to estrogen-induced binding. Moreover, we found that siRNA-mediated downregulation of ER? in absence of estrogen is accompanied by changes in the expression levels of hundreds of coding and noncoding RNAs. Downregulated mRNAs showed enrichment in genes related to epithelial cell growth and development. Stable ER? downregulation using shRNA, which caused cell-growth arrest, was accompanied by increased H3K27me3 at ER? binding sites. Finally, we found that FOXA1 and AP2? binding to several sites is decreased upon ER? silencing, suggesting that unliganded ER? participates, together with other factors, to the maintenance of the luminal-specific cistrome in breast cancer cells. Examination of unligandend estrogen receptor alpha (apoER?) DNA interactions in control and ER? siRNA treated MCF7 cells.
2014-03-03 | E-GEOD-53531 | biostudies-arrayexpress
Project description:Estrogen receptor beta (ERbeta) has potent anti-proliferative and anti-inflammatory properties, suggesting that ER beta-selective agonists might be a new class of therapeutic and chemopreventative agents. To understand how ER beta regulates genes, we identified genes regulated by the unliganded and liganded forms of ER alpha and ER beta in U2OS cells. Microarray data demonstrated that virtually no gene regulation occurred with unliganded ER alpha, whereas many genes were regulated by estradiol (E2). These results demonstrate ER alpha requires a ligand to regulate a single class of genes. In contrast, ER beta regulated three classes of genes. Class I genes were regulated primarily by unliganded ER beta. Class II genes were regulated only with E2, whereas Class III genes were regulated by both unliganded ER beta and E2. There were 453 Class I genes, 258 Class II genes and 83 Class III genes. To explore the mechanism whereby ER beta regulates different classes of genes ChIP-seq was performed to identify ER beta binding sites and adjacent transcription factor motifs in regulated genes. AP1 binding sites were more enriched in Class I genes, whereas ERE, NFKB1 and SP1 sites were more enriched in class II genes. ER beta bound to all three classes of genes demonstrating that ER beta binding is not responsible for differential regulation of genes by unliganded and liganded ER beta. The coactivator, NCOA2 was differentially recruited to several target genes. Our findings indicate that the unliganded and liganded forms of ER beta regulate three classes of genes by interacting with different transcription factors and coactivators. Examination of ER beta binding sites in U2OS cells with or without E2 treatment
2010-05-12 | E-GEOD-21770 | biostudies-arrayexpress
Project description:Estrogen receptorï? beta (ER beta) has potent anti-proliferative and anti-inflammatory properties, suggesting that ER beta-selective agonists might be a new class of therapeutic and chemopreventative agents. To understand how ER beta regulates genes, we identified genes regulated by the unliganded and liganded forms of ER alpha and ER beta in U2OS cells. Microarray data demonstrated that virtually no gene regulation occurred with unliganded ER alpha, whereas many genes were regulated by estradiol (E2). These results demonstrate ER alpha requires a ligand to regulate a single class of genes. In contrast, ER beta regulated three classes of genes. Class I genes were regulated primarily by unliganded ER beta. Class II genes were regulated only with E2, whereas Class III genes were regulated by both unliganded ER beta and E2. There were 453 Class I genes, 258 Class II genes and 83 Class III genes. To explore the mechanism whereby ER beta regulates different classes of genes ChIP-seq was performed to identify ER beta binding sites and adjacent transcription factor motifs in regulated genes. AP1 binding sites were more enriched in Class I genes, whereas ERE, NFKB1 and SP1 sites were more enriched in class II genes. ER beta bound to all three classes of genes demonstrating that ER beta binding is not responsible for differential regulation of genes by unliganded and liganded ER beta. The coactivator, NCOA2 was differentially recruited to several target genes. Our findings indicate that the unliganded and liganded forms of ER beta regulate three classes of genes by interacting with different transcription factors and coactivators. U2OS cell lines are stably transfected with a doxycycline-inducible ER alpha or beta. 18 samples are analyzed with triplicate for each of the 6 conditions. The 6 conditions include ER alpha transfected without doxycycline added, ER alpha transfected with doxycycline added, ER alpha transfected with doxycycline added and E2 treatment, ER beta transfected without doxycycline added, ER beta transfected with doxycycline added, and ER beta transfected with doxycycline added and E2 treatment.
2010-05-28 | E-GEOD-21769 | biostudies-arrayexpress
Project description:Cross-talk between Estrogen Receptor-related Receptor alpha (ERRalpha) and Estrogen Receptor (ERalpha) pathways.
| PRJNA106665 | ENA
Project description:Estrogen receptor beta (ERbeta) has potent anti-proliferative and anti-inflammatory properties, suggesting that ER beta-selective agonists might be a new class of therapeutic and chemopreventative agents. To understand how ER beta regulates genes, we identified genes regulated by the unliganded and liganded forms of ER alpha and ER beta in U2OS cells. Microarray data demonstrated that virtually no gene regulation occurred with unliganded ER alpha, whereas many genes were regulated by estradiol (E2). These results demonstrate ER alpha requires a ligand to regulate a single class of genes. In contrast, ER beta regulated three classes of genes. Class I genes were regulated primarily by unliganded ER beta. Class II genes were regulated only with E2, whereas Class III genes were regulated by both unliganded ER beta and E2. There were 453 Class I genes, 258 Class II genes and 83 Class III genes. To explore the mechanism whereby ER beta regulates different classes of genes ChIP-seq was performed to identify ER beta binding sites and adjacent transcription factor motifs in regulated genes. AP1 binding sites were more enriched in Class I genes, whereas ERE, NFKB1 and SP1 sites were more enriched in class II genes. ER beta bound to all three classes of genes demonstrating that ER beta binding is not responsible for differential regulation of genes by unliganded and liganded ER beta. The coactivator, NCOA2 was differentially recruited to several target genes. Our findings indicate that the unliganded and liganded forms of ER beta regulate three classes of genes by interacting with different transcription factors and coactivators.
2010-05-12 | GSE21770 | GEO
Project description:Estrogen receptor beta (ERbeta) has potent anti-proliferative and anti-inflammatory properties, suggesting that ER beta-selective agonists might be a new class of therapeutic and chemopreventative agents. To understand how ER beta regulates genes, we identified genes regulated by the unliganded and liganded forms of ER alpha and ER beta in U2OS cells. Microarray data demonstrated that virtually no gene regulation occurred with unliganded ER alpha, whereas many genes were regulated by estradiol (E2). These results demonstrate ER alpha requires a ligand to regulate a single class of genes. In contrast, ER beta regulated three classes of genes. Class I genes were regulated primarily by unliganded ER beta. Class II genes were regulated only with E2, whereas Class III genes were regulated by both unliganded ER beta and E2. There were 453 Class I genes, 258 Class II genes and 83 Class III genes. To explore the mechanism whereby ER beta regulates different classes of genes ChIP-seq was performed to identify ER beta binding sites and adjacent transcription factor motifs in regulated genes. AP1 binding sites were more enriched in Class I genes, whereas ERE, NFKB1 and SP1 sites were more enriched in class II genes. ER beta bound to all three classes of genes demonstrating that ER beta binding is not responsible for differential regulation of genes by unliganded and liganded ER beta. The coactivator, NCOA2 was differentially recruited to several target genes. Our findings indicate that the unliganded and liganded forms of ER beta regulate three classes of genes by interacting with different transcription factors and coactivators.
2010-05-12 | GSE21769 | GEO