Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA136037 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Integrative model of genomic factors for determining binding site selection by estrogen receptor alpha in MCF-7 cancer cells
| PRJNA130905 | ENA
Project description:[E-MTAB-131] Estrogen Receptor alpha estrogen-responsive binding sites in MCF-7
| PRJNA135831 | ENA
Project description:Estrogen-responsive Estrogen Receptor alpha binding sites in MCF-7 by ChIP-seq
| PRJNA150381 | ENA
Project description:Estrogen has vascular protective effects in premenopausal women and in women under 60 receiving hormone replacement therapy. However, estrogen also increases risks of breast and uterine cancers and of venous thromboses linked to upregulation of coagulation factors in the liver. In mouse models, the vasoprotective effects of estrogen are mediated by the estrogen receptor alpha (ERa) transcription factor. Here, through next generation sequencing approaches, we show that almost all of the genes regulated by 17-b-estradiol (E2) differ between mouse aorta and mouse liver, and that this is associated with a distinct genomewide distribution of ERa on chromatin. Bioinformatic analysis of E2-regulated promoters and ERa binding site sequences identify several transcription factors that may determine the tissue specificity of ERa binding and E2-regulated genes, including the enrichment of NFkB, AML1 and AP-1 sites in the promoters of E2 downregulated inflammatory genes in aorta but not liver. The possible vascular-specific functions of these factors suggests ways in which the protective effects of estrogen could be promoted in the vasculature without incurring negative effects in other tissues. Our results also highlight the likely importance of rapid signaling of membrane-associated ERa to cellular kinases (altering the activities of transcription factors other than ER itself) in determining tissue specific transcriptional responses to estrogen. The aortas or liver fragments of wild-type C57/BL6 mice were incubated ex vivo with 10nM E2 or ethanol vehicle for 45 minutes before formaldehyde fixation, harvesting of chromatin & ChIP with anti- mouse estrogen receptor alpha antibodies. Each condition was performed with two biological replicates, and each replicate contained aortas or liver fragments from 5 mice.
2014-06-30 | E-GEOD-52351 | biostudies-arrayexpress
Project description:Retinoic acid receptor-alpha (RAR alpha) is a known estrogen target gene in breast cancer cells. The consequence of RAR alpha induction by estrogen was previously unknown. We now show that RAR alpha is required for efficient estrogen receptor-alpha (ER)-mediated transcription and cell proliferation. RAR alpha can interact with ER-binding sites, but this occurs in an ER-dependent manner, providing a novel role for RAR alpha that is independent of its classic role. We show, on a genome-wide scale, that RAR alpha and ER can co-occupy regulatory regions together within the chromatin. This transcriptionally active co-occupancy and dependency occurs when exposed to the predominant breast cancer hormone, estrogen--an interaction that is promoted by the estrogen-ER induction of RAR alpha. These findings implicate RAR alpha as an essential component of the ER complex, potentially by maintaining ER-cofactor interactions, and suggest that different nuclear receptors can cooperate for effective transcriptional activity in breast cancer cells. RAR alpha silenced breast cancer MCF-7 cell lines or control siRNA in the presence of estrogen or a vehicle. MCF-7 cells were hormone-depleted for 3 d and treated with 100 nM estrogen for 12 h. There were three biological replicates for each of the four different groups.
2010-06-16 | E-GEOD-22213 | biostudies-arrayexpress
Project description:Most human transcription factors bind a small subset of potential genomic sites and often use different subsets in different cell types. To identify mechanisms that govern cell type-specific transcription factor binding, we used an integrative approach to study estrogen receptor α (ER). We found that ER exhibits two distinct modes of binding. Shared sites, bound in multiple cell types, are characterized by high affinity estrogen response elements (EREs), inaccessible chromatin and a lack of DNA methylation, while cell-specific sites are characterized by a lack of EREs, co-occurrence with other transcription factors and cell type-specific chromatin accessibility and DNA methylation. These observations enabled accurate quantitative models of ER binding that suggest tethering of ER to one-third of cell-specific sites. The distinct properties of cell-specific binding were also observed with glucocorticoid receptor and for ER in primary mouse tissues, representing an elegant genomic encoding scheme for generating cell type-specific gene regulation. ChIP-seq of transcription factors in mouse tissues
2013-12-31 | E-GEOD-49993 | biostudies-arrayexpress
Project description:Identification of Estrogen Receptor alpha (ERa) binding sites by ChIP-seq in MCF-7 breast cancer cells following an estrogen treatment. This study describes molecular effects of estradiol treatment and subsequent regulation by ER for a single gene/locus. A public ER chipseq (available in SRA as ERR011973), in addition to our own data, guided us to regulatory regions were ER was binding that were then analyzed in detail using "manual" ChIP. MCF-7 cells were treated for 1 h either 10 nm estradiol (E2) or vehicle (ethanol) and subjected to ChIP using antibodies against ERa or IgG.
2012-12-17 | E-GEOD-34759 | biostudies-arrayexpress
Project description:Estrogen has vascular protective effects in premenopausal women and in women under 60 receiving hormone replacement therapy. However, estrogen also increases risks of breast and uterine cancers and of venous thromboses linked to upregulation of coagulation factors in the liver. In mouse models, the vasoprotective effects of estrogen are mediated by the estrogen receptor alpha (ERa) transcription factor. Here, through next generation sequencing approaches, we show that almost all of the genes regulated by 17-b-estradiol (E2) differ between mouse aorta and mouse liver, and that this is associated with a distinct genomewide distribution of ERa on chromatin. Bioinformatic analysis of E2-regulated promoters and ERa binding site sequences identify several transcription factors that may determine the tissue specificity of ERa binding and E2-regulated genes, including the enrichment of NFkB, AML1 and AP-1 sites in the promoters of E2 downregulated inflammatory genes in aorta but not liver. The possible vascular-specific functions of these factors suggests ways in which the protective effects of estrogen could be promoted in the vasculature without incurring negative effects in other tissues. Our results also highlight the likely importance of rapid signaling of membrane-associated ERa to cellular kinases (altering the activities of transcription factors other than ER itself) in determining tissue specific transcriptional responses to estrogen. The aortas or liver fragments of wild-type C57/BL6 mice were incubated ex vivo with 10nM E2 or ethanol vehicle for 4 hours before harvesting for RNA collection. Each condition was performed with two biological replicates, and each replicate contained aortas or liver fragments from 4 mice.
2014-06-30 | E-GEOD-57804 | biostudies-arrayexpress
Project description:Estrogen receptor-α (ERα) is an important driver of breast cancer and is the target for hormonal therapies, anti-estrogens and drugs that limit estrogen biosynthesis (aromatase inhibitors). Mutations in the ESR1 gene identified in metastatic breast cancer provide a potential mechanism for acquired resistance to hormone therapies. We have used CRISPR-Cas9 mediated genome editing in the MCF-7 breast cancer cell line, generating MCF-7-Y537S. MCF-7-Y537S cells encode a wild-type (tyrosine 537) and a mutant (serine 537) allele. Growth of the line is estrogen-independent and expression of ERα target genes is elevated in the absence of estrogen. ER ChIP-seq was carried out to map global ERα binding sites in the presence and absence of estrogen. RNA-seq following estrogen treatment was used for gene expression analysis. We show that expression of ER target genes and ER recruitment to ER binding regions is similar in MCF-7 and MCF-7-Y537S cells, except that ER recruitment to DNA and expression of ER target genes is frequently elevated in the absence of estrogen.
2016-10-25 | GSE78285 | GEO
Project description:Estrogen receptor-α (ERα) is an important driver of breast cancer and is the target for hormonal therapies, anti-estrogens and drugs that limit estrogen biosynthesis (aromatase inhibitors). Mutations in the ESR1 gene identified in metastatic breast cancer provide a potential mechanism for acquired resistance to hormone therapies. We have used CRISPR-Cas9 mediated genome editing in the MCF-7 breast cancer cell line, generating MCF-7-Y537S. MCF-7-Y537S cells encode a wild-type (tyrosine 537) and a mutant (serine 537) allele. Growth of the line is estrogen-independent and expression of ERα target genes is elevated in the absence of estrogen. ER ChIP-seq was carried out to map global ERα binding sites in the presence and absence of estrogen. RNA-seq following estrogen treatment was used for gene expression analysis. We show that expression of ER target genes and ER recruitment to ER binding regions is similar in MCF-7 and MCF-7-Y537S cells, except that ER recruitment to DNA and expression of ER target genes is frequently elevated in the absence of estrogen
2016-10-25 | GSE78284 | GEO