Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA255508 | ENA |
REPOSITORIES: ENA
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Project description:TNFα Signaling Exposes Latent Estrogen Receptor Binding Sites in Breast Cancer Cells [ChIP-seq]
| PRJNA255509 | ENA
Project description:The interplay between mitogenic and proinflammatory signaling pathways play key roles in determining the phenotypes and clinical outcomes of breast cancers. We have used global nuclear run-on coupled with deep sequencing to characterize the immediate transcriptional responses of MCF-7 breast cancer cells treated with estradiol, TNFα, or both. In addition, we have integrated these data with chromatin immunoprecipitation coupled with deep sequencing for estrogen receptor alpha (ERα), the pioneer factor FoxA1 and the p65 subunit of the NF-κB transcription factor. Our results indicate extensive transcriptional interplay between these two signaling pathways, which is observed for a number of classical mitogenic and proinflammatory protein-coding genes. In addition, GRO-seq has allowed us to capture the transcriptional crosstalk at the genomic locations encoding for long non-coding RNAs, a poorly characterized class of RNAs which have been shown to play important roles in cancer outcomes. The synergistic and antagonistic interplay between estrogen and TNFα signaling at the gene level is also evident in the patterns of ERα and NF-κB binding, which relocalize to new binding sites that are not occupied by either treatment alone. Interestingly, the chromatin accessibility of classical ERα binding sites is predetermined prior to estrogen treatment, whereas ERα binding sites gained upon co-treatment with TNFα require NF-κB and FoxA1 to promote chromatin accessibility de novo. Our data suggest that TNFα signaling recruits FoxA1 and NF-κB to latent ERα enhancer locations and directly impact ERα enhancer accessibility. Binding of ERα to latent enhancers upon co-treatment, results in increased enhancer transcription, target gene expression and altered cellular response. This provides a mechanistic framework for understanding the molecular basis for integration of mitogenic and proinflammatory signaling in breast cancer.
2015-03-05 | GSE59531 | GEO
Project description:The interplay between mitogenic and proinflammatory signaling pathways play key roles in determining the phenotypes and clinical outcomes of breast cancers. We have used global nuclear run-on coupled with deep sequencing to characterize the immediate transcriptional responses of MCF-7 breast cancer cells treated with estradiol, TNF?, or both. In addition, we have integrated these data with chromatin immunoprecipitation coupled with deep sequencing for estrogen receptor alpha (ER?), the pioneer factor FoxA1 and the p65 subunit of the NF-?B transcription factor. Our results indicate extensive transcriptional interplay between these two signaling pathways, which is observed for a number of classical mitogenic and proinflammatory protein-coding genes. In addition, GRO-seq has allowed us to capture the transcriptional crosstalk at the genomic locations encoding for long non-coding RNAs, a poorly characterized class of RNAs which have been shown to play important roles in cancer outcomes. The synergistic and antagonistic interplay between estrogen and TNF? signaling at the gene level is also evident in the patterns of ER? and NF-?B binding, which relocalize to new binding sites that are not occupied by either treatment alone. Interestingly, the chromatin accessibility of classical ER? binding sites is predetermined prior to estrogen treatment, whereas ER? binding sites gained upon co-treatment with TNF? require NF-?B and FoxA1 to promote chromatin accessibility de novo. Our data suggest that TNF? signaling recruits FoxA1 and NF-?B to latent ER? enhancer locations and directly impact ER? enhancer accessibility. Binding of ER? to latent enhancers upon co-treatment, results in increased enhancer transcription, target gene expression and altered cellular response. This provides a mechanistic framework for understanding the molecular basis for integration of mitogenic and proinflammatory signaling in breast cancer. Using GRO-seq and ChIP-seq (ER, FoxA1 and p65) to assay the molecular crosstalk of MCF-7 cells treated with E2, TNFa or both E2+TNFa.
2015-03-05 | E-GEOD-59530 | biostudies-arrayexpress
Project description:The interplay between mitogenic and proinflammatory signaling pathways play key roles in determining the phenotypes and clinical outcomes of breast cancers. We have used global nuclear run-on coupled with deep sequencing to characterize the immediate transcriptional responses of MCF-7 breast cancer cells treated with estradiol, TNFM-NM-1, or both. In addition, we have integrated these data with chromatin immunoprecipitation coupled with deep sequencing for estrogen receptor alpha (ERM-NM-1), the pioneer factor FoxA1 and the p65 subunit of the NF-M-NM-:B transcription factor. Our results indicate extensive transcriptional interplay between these two signaling pathways, which is observed for a number of classical mitogenic and proinflammatory protein-coding genes. In addition, GRO-seq has allowed us to capture the transcriptional crosstalk at the genomic locations encoding for long non-coding RNAs, a poorly characterized class of RNAs which have been shown to play important roles in cancer outcomes. The synergistic and antagonistic interplay between estrogen and TNFM-NM-1 signaling at the gene level is also evident in the patterns of ERM-NM-1 and NF-M-NM-:B binding, which relocalize to new binding sites that are not occupied by either treatment alone. Interestingly, the chromatin accessibility of classical ERM-NM-1 binding sites is predetermined prior to estrogen treatment, whereas ERM-NM-1 binding sites gained upon co-treatment with TNFM-NM-1 require NF-M-NM-:B and FoxA1 to promote chromatin accessibility de novo. Our data suggest that TNFM-NM-1 signaling recruits FoxA1 and NF-M-NM-:B to latent ERM-NM-1 enhancer locations and directly impact ERM-NM-1 enhancer accessibility. Binding of ERM-NM-1 to latent enhancers upon co-treatment, results in increased enhancer transcription, target gene expression and altered cellular response. This provides a mechanistic framework for understanding the molecular basis for integration of mitogenic and proinflammatory signaling in breast cancer. Using GRO-seq and ChIP-seq (ER, FoxA1 and p65) to assay the molecular crosstalk of MCF-7 cells treated with E2, TNFM-NM-1 or both E2+TNFM-NM-1.
2015-03-05 | E-GEOD-59531 | biostudies-arrayexpress
Project description:The interplay between mitogenic and proinflammatory signaling pathways play key roles in determining the phenotypes and clinical outcomes of breast cancers. We have used global nuclear run-on coupled with deep sequencing to characterize the immediate transcriptional responses of MCF-7 breast cancer cells treated with estradiol, TNF?, or both. In addition, we have integrated these data with chromatin immunoprecipitation coupled with deep sequencing for estrogen receptor alpha (ER?), the pioneer factor FoxA1 and the p65 subunit of the NF-?B transcription factor. Our results indicate extensive transcriptional interplay between these two signaling pathways, which is observed for a number of classical mitogenic and proinflammatory protein-coding genes. In addition, GRO-seq has allowed us to capture the transcriptional crosstalk at the genomic locations encoding for long non-coding RNAs, a poorly characterized class of RNAs which have been shown to play important roles in cancer outcomes. The synergistic and antagonistic interplay between estrogen and TNF? signaling at the gene level is also evident in the patterns of ER? and NF-?B binding, which relocalize to new binding sites that are not occupied by either treatment alone. Interestingly, the chromatin accessibility of classical ER? binding sites is predetermined prior to estrogen treatment, whereas ER? binding sites gained upon co-treatment with TNF? require NF-?B and FoxA1 to promote chromatin accessibility de novo. Our data suggest that TNF? signaling recruits FoxA1 and NF-?B to latent ER? enhancer locations and directly impact ER? enhancer accessibility. Binding of ER? to latent enhancers upon co-treatment, results in increased enhancer transcription, target gene expression and altered cellular response. This provides a mechanistic framework for understanding the molecular basis for integration of mitogenic and proinflammatory signaling in breast cancer.
2015-03-05 | GSE59530 | GEO
Project description:In this study, we used Global Run-On sequencing (GRO-seq), a method that assays the genome-wide location and orientation of all active RNA polymerases. We generated a global profile of active transcription at ERM-NM-1 binding sites in MCF-7 human breast cancer cells in response to short time course of E2 treatment. This method enabled us to detect active transcription at enhancers and define a class of primary transcripts transcribed uni- or bidirectionally from the ERM-NM-1 binding sites. The raw data used in this study is from GSE27463 but sequenced to a greater depth. Using GRO-seq over a time course (0, 10, 40 min) of estrogen signaling in ER-alpha positive MCF-7 human breast cancer cells.
2013-05-08 | E-GEOD-43835 | biostudies-arrayexpress
Project description:The estrogen receptor is the master transcriptional regulator of breast cancer phenotype and the archetype of a molecular therapeutic target. We mapped all estrogen receptor and RNA polymerase II binding sites on a genome-wide scale, identifying the authentic cis binding sites and target genes, in breast cancer cells. Combining this unique resource with gene expression data demonstrates distinct temporal mechanisms of estrogen-mediated gene regulation,particularly in the case of estrogen-suppressed genes. Furthermore, this resource has allowed the identification of cis-regulatory sites in previously unexplored regions of the genome and the cooperating transcription factors underlying estrogen signaling in breast cancer. Keywords: estrogen effect, time course
2008-05-02 | GSE11324 | GEO
Project description:The estrogen receptor is the master transcriptional regulator of breast cancer phenotype and the archetype of a molecular therapeutic target. We mapped all estrogen receptor and RNA polymerase II binding sites on a genome-wide scale, identifying the authentic cis binding sites and target genes, in breast cancer cells. Combining this unique resource with gene expression data demonstrates distinct temporal mechanisms of estrogen-mediated gene regulation,particularly in the case of estrogen-suppressed genes. Furthermore, this resource has allowed the identification of cis-regulatory sites in previously unexplored regions of the genome and the cooperating transcription factors underlying estrogen signaling in breast cancer. Experiment Overall Design: This Series currently contains the gene expression data accompaning Carroll JS et al. Nature Genetics 38,1289-1297(2006). MCF7 cells were stimulated with 100 nM estrogen for 0, 3, 6, or 12h. All experiments were performed in triplicate.
2008-06-11 | E-GEOD-11324 | biostudies-arrayexpress