Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE27824
PROVIDER: PRJNA141877 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Reprogramming Transcriptional Responses through Functionally-Distinct Classes of Enhancers in Prostate Cancer Cells
| PRJNA137903 | ENA
Project description:Reprogramming Transcriptional Responses through Functionally-Distinct Classes of Enhancers in Prostate Cancer Cells [ChIP-Seq, Gro-Seq]
| PRJNA141903 | ENA
Project description:Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell type-specific gene expression programs; however, the potential that there are pre-established enhancers in different functional classes that permit alternative signal-dependent transcriptional responses has remained unexplored. Here we present evidence that cell lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), acting at structurally- and functionally-distinct classes of pre-established enhancers, thus licensing specific signal-activated responses while restricting others. Consequently, FoxA1 down-regulation, an unfavorable prognostic sign in advanced prostate tumors, causes a massive switch in AR binding from one functional class of enhancers to another, with a parallel switch in levels of enhancer-templated non-coding RNAs (eRNAs) revealed by the global run-on assay (GRO-seq), which documents the dramatic reprogramming of the hormonal response. The molecular basis for this switch lies in the release of FoxA1-mediated restriction of AR binding to the new enhancer class with no apparent nucleosome remodeling, which is required for stimulating their eRNA transcription and/or enhancing enhancer:promoter looping and gene activation. Together, these findings reveal a large repository of pre-determined enhancers in the human genome that can be dynamically tuned to induce their transcription and activation of alternative gene expression programs, which may underlie many sequential gene expression events in development or during disease progression. ChIP-Seq, Gro-Seq, and gene expression profiling was performed in LNCaP cells with hormone treatment and siRNA against FoxA1. Gene expression profiling data presented here.
2011-05-15 | E-GEOD-27682 | biostudies-arrayexpress
Project description:Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell type-specific gene expression programs; however, the potential that there are pre-established enhancers in different functional classes that permit alternative signal-dependent transcriptional responses has remained unexplored. Here we present evidence that cell lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), acting at structurally- and functionally-distinct classes of pre-established enhancers, thus licensing specific signal-activated responses while restricting others. Consequently, FoxA1 down-regulation, an unfavorable prognostic sign in advanced prostate tumors, causes a massive switch in AR binding from one functional class of enhancers to another, with a parallel switch in levels of enhancer-templated non-coding RNAs (eRNAs) revealed by the global run-on assay (GRO-seq), which documents the dramatic reprogramming of the hormonal response. The molecular basis for this switch lies in the release of FoxA1-mediated restriction of AR binding to the new enhancer class with no apparent nucleosome remodeling, which is required for stimulating their eRNA transcription and/or enhancing enhancer:promoter looping and gene activation. Together, these findings reveal a large repository of pre-determined enhancers in the human genome that can be dynamically tuned to induce their transcription and activation of alternative gene expression programs, which may underlie many sequential gene expression events in development or during disease progression. ChIP-Seq, Gro-Seq, and gene expression profiling was performed in LNCaP cells with hormone treatment and siRNA against FoxA1 ChIP-Seq and Gro-Seq data presented here. Supplementary file GroSeq.denovo.transcripts.hg18.bed represents analysis using GSM686948-GSM686950.
2011-05-15 | E-GEOD-27823 | biostudies-arrayexpress
Project description:Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell type-specific gene expression programs; however, the potential that there are pre-established enhancers in different functional classes that permit alternative signal-dependent transcriptional responses has remained unexplored. Here we present evidence that cell lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), acting at structurally- and functionally-distinct classes of pre-established enhancers, thus licensing specific signal-activated responses while restricting others. Consequently, FoxA1 down-regulation, an unfavorable prognostic sign in advanced prostate tumors, causes a massive switch in AR binding from one functional class of enhancers to another, with a parallel switch in levels of enhancer-templated non-coding RNAs (eRNAs) revealed by the global run-on assay (GRO-seq), which documents the dramatic reprogramming of the hormonal response. The molecular basis for this switch lies in the release of FoxA1-mediated restriction of AR binding to the new enhancer class with no apparent nucleosome remodeling, which is required for stimulating their eRNA transcription and/or enhancing enhancer:promoter looping and gene activation. Together, these findings reveal a large repository of pre-determined enhancers in the human genome that can be dynamically tuned to induce their transcription and activation of alternative gene expression programs, which may underlie many sequential gene expression events in development or during disease progression.
2011-05-15 | GSE27823 | GEO
Project description:Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell type-specific gene expression programs; however, the potential that there are pre-established enhancers in different functional classes that permit alternative signal-dependent transcriptional responses has remained unexplored. Here we present evidence that cell lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), acting at structurally- and functionally-distinct classes of pre-established enhancers, thus licensing specific signal-activated responses while restricting others. Consequently, FoxA1 down-regulation, an unfavorable prognostic sign in advanced prostate tumors, causes a massive switch in AR binding from one functional class of enhancers to another, with a parallel switch in levels of enhancer-templated non-coding RNAs (eRNAs) revealed by the global run-on assay (GRO-seq), which documents the dramatic reprogramming of the hormonal response. The molecular basis for this switch lies in the release of FoxA1-mediated restriction of AR binding to the new enhancer class with no apparent nucleosome remodeling, which is required for stimulating their eRNA transcription and/or enhancing enhancer:promoter looping and gene activation. Together, these findings reveal a large repository of pre-determined enhancers in the human genome that can be dynamically tuned to induce their transcription and activation of alternative gene expression programs, which may underlie many sequential gene expression events in development or during disease progression.
2011-05-15 | GSE27682 | GEO
Project description:The integrated activity of cis-regulatory elements fine-tunes transcriptional programs of mammalian cells by recruiting cell type–specific as well as ubiquitous transcription factors (TFs). Despite their key role in modulating transcription, enhancers are still poorly characterized at the molecular level, and their limited DNA sequence conservation in evolution and variable distance from target genes make their unbiased identification challenging. The coexistence of high mono-methylation and low tri-methylation levels of lysine 4 of histone H3 is considered a signature of enhancers, but a comprehensive view of histone modifications associated to enhancers is still lacking. By combining chromatin immunoprecipitation (ChIP) with mass spectrometry, we investigated cis-regulatory regions in macrophages to comprehensively identify histone marks specifically associated with enhancers, and to profile their dynamics after transcriptional activation elicited by an inflammatory stimulation. The intersection of the proteomics data with ChIP-seq and RNA-seq analyses revealed the existence of novel subpopulations of enhancers, marked by specific histone modification signatures: specifically, H3K36me2/K4me1 marks transcribed enhancers, while H3K36me3/K4me1 and H3K79me2/K4me1 combinations mark distinct classes of intronic enhancers. Thus, our MS analysis of functionally distinct genomic regions revealed the combinatorial code of histone modifications, highlighting the potential of proteomics in addressing fundamental questions in epigenetics.
2017-10-09 | PXD007582 | Pride
Project description:The integration of diverse ‘omic’ datasets will increase our understanding of the key signaling pathways that drive disease. Here, we used clinical tissue cohorts corresponding to lethal metastatic castration resistant prostate cancer (CRPC) obtained at rapid autopsy to integrate mutational, transcriptomic, and phosphoproteomic datasets for pathway analysis. Using Tied Diffusion through Interacting Events (TieDIE), we integrated differentially expressed transcriptional master regulators, functionally mutated genes, and differentially ‘activated’ kinases in CRPC tissues to synthesize a robust signaling network consisting of pathways with known and novel gene interactions. For 6 individual CRPC patients for which we had transcriptomic and phosphoproteomic data we observed distinct pathway activation states for each patient profile. In one patient, the activated pathways were strikingly similar to a prostate cancer cell line, 22Rv1, providing us with a good pre-clinical model to test targeted, combination therapies. In all, synthesis of multiple ‘omic’ datasets revealed a plethora of pathway information suitable for targeted therapies in lethal prostate cancer.
2016-08-19 | PXD002286 | Pride
Project description:The integration of diverse ‘omic’ datasets will increase our understanding of the key signaling pathways that drive disease. Here, we used clinical tissue cohorts corresponding to lethal metastatic castration resistant prostate cancer (CRPC) obtained at rapid autopsy to integrate mutational, transcriptomic, and phosphoproteomic datasets for pathway analysis. Using Tied Diffusion through Interacting Events (TieDIE), we integrated differentially expressed transcriptional master regulators, functionally mutated genes, and differentially ‘activated’ kinases in CRPC tissues to synthesize a robust signaling network consisting of pathways with known and novel gene interactions. For 6 individual CRPC patients for which we had transcriptomic and phosphoproteomic data we observed distinct pathway activation states for each patient profile. In one patient, the activated pathways were strikingly similar to a prostate cancer cell line, 22Rv1, providing us with a good pre-clinical model to test targeted, combination therapies. In all, synthesis of multiple ‘omic’ datasets revealed a plethora of pathway information suitable for targeted therapies in lethal prostate cancer.
2017-03-29 | MSV000080776 | MassIVE
Project description:Embryonic stem cells (ESCs) can be maintained in the naïve state through inhibition of Mek1/2 and Gsk3 (2i). A relevant effect of 2i is the inhibition of Cdk8/19, which are negative regulators of the Mediator complex, responsible for the activity of enhancers. Inhibition of Cdk8/19 (Cdk8/19i) stimulates enhancers and, similar to 2i, stabilizes ESCs in the naïve state. Here, we use mass spectrometry to describe the molecular events (phosphoproteome, proteome, and metabolome) triggered by 2i and Cdk8/19i on ESCs. Our data reveal widespread commonalities between these two treatments, suggesting overlapping processes. We find that post-transcriptional de-repression by both 2i and Cdk8/19i might support the mitochondrial capacity of naive cells. However, proteome reprogramming in each treatment is achieved by different mechanisms. Cdk8/19i acts directly on the transcriptional machinery, activating key identity genes to promote the naïve program. In contrast, 2i stabilizes the naïve circuitry through, in part, de-phosphorylation of downstream transcriptional effectors.
2021-02-10 | MTBLS301 | MetaboLights