The landscape of enhancer transcription in prostate cancer [RNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE221107 | GEO | 2025/02/09
REPOSITORIES: GEO
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Project description:Current genome-wide detection of chromatin accessibility uses the assay for transposase-accessible chromatin (ATAC-seq). To a provide panoramic view of the chromatin accessibility landscape in prostate cancer and normal prostate, we performed ATAC-seq in 20 pairs of prostate cancer tissues and matched adjacent tissues. Assay of transposase accessible chromatin with high-throughput sequencing (ATAC-seq) for 20 pairs of prostate cancer tissues and matched adjacent tissues.
2025-02-09 | GSE221108 | GEO
Project description:Recent studies suggest a hierarchical model in which lineage-determining factors act in a collaborative manner to select and prime cell-specific enhancers, thereby enabling signal-dependent transcription factors to bind and function in a cell type-specific manner. Consistent with this model, TLR4 signaling primarily regulates macrophage gene expression through a pre-existing enhancer landscape. However, TLR4 signaling also induces priming of ~3000 enhancer-like regions de novo, enabling visualization of intermediates in enhancer selection and activation. Unexpectedly, we find that enhancer transcription precedes local mono- and di-methylation of histone H3 lysine 4 (H3K4me1/2). H3K4 methylation at de novo enhancers is primarily dependent on the histone methyltransferases Mll1, Mll2/4 and Mll3, and is significantly reduced by inhibition of RNA polymerase II elongation. Collectively, these findings suggest an essential role of enhancer transcription in H3K4me1/2 deposition at de novo enhancers that is independent of potential functions of the resulting eRNA transcripts. ChIP-Seq and Gro-Seq profiling was performed in thioglycollate-elicited peritoneal macrophages, PU.1-/- and PUER cells treated as indicated.
2013-08-09 | E-GEOD-48759 | biostudies-arrayexpress
Project description:High-fat diet and obesity are high risk factors for colorectal cancer. The underlying mechanism is still unclear. Environmental factors alter the epigenome to affect gene expression thus the phenotype. In response to external stimuli, the cis-regulatory regions, especially enhancer loci, are key elements for regulating selective gene expression. We thus explored the effects of high-fat diet and the accompanying obesity on gene expression and the enhancer landscape in colon epithelium. High-fat diet exposed binding sites of transcription factors downstream of signaling pathways important in the initiation and progression of colon cancer. Meantime, colon-specific enhancers were lost rendering the cells potential for dedifferentiation. The alteration at enhancer regions drives a specific transcription program promoting colon cancer progression. The comprehensive interrogation of enhancer changes by high-fat diet in colon epithelium provides a number of insights into the underlying biology of high-fat diet and obesity in increasing colon cancer risk, and provides potential therapeutic targets to treat obese colon cancer patients. We measured gene expression in colon epithelium from wild type mice and NAG-1 (non-steroidal anti-inflammatory drug (NSAID)-activated gene-1) transgenic mice fed either a 10% fat diet (LF) or a 60% fat diet (HF) for 20 weeks, using Agilent Whole Mouse Genome 4x44 multiplex format oligo arrays (014868) (Agilent Technologies) following the Agilent 1-color microarray-based gene expression analysis protocol. The ChIP-seq component of the study is included in GSE46748.
2014-01-13 | E-GEOD-46843 | biostudies-arrayexpress
Project description:Purpose: Examine H3K27ac enhancer and super-enhancer landscape differences between primary colorectal carcinoma and adjacent normal mucosa towards the identification of novel downstream targets. Methods: H3K27ac ChIP-seq and RNA-seq were performed on fresh primary colorectal carcinoma samples and normal colonic mucosa, from human patient samples. Results: We identified 2026 total super-enhancers in our cohort, between primary colorectal and normal mucosa. We quantified differences in H3K27ac signal within this space, between tumor and normal, and identified putative downstream target genes through integration with sample matched RNA-seq using a positive linear correlation model to identifty putative target genes.
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Project description:CircRNA sequencing was performed on 5 pairs of giant cell tumors of bone and their adjacent tissues.
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Project description:Transcription is a ubiquitous feature of active enhancers, yet the regulatory role of enhancer transcription or transcripts remains debated. Here, we depleted the RNA polymerase II pausing and elongation factor Spt5 in activated mouse B cells and found that approximately 50% of enhancer-gene pairs showed correlated changes in transcription, consistent with a potential functional requirement for enhancer transcription. In particular, Spt5 depletion led to loss of super-enhancer-promoter physical interaction and gene expression at the immunoglobulin heavy chain locus (Igh), abrogating antibody class switch recombination. This defect correlated strictly with loss of enhancer transcription and did not affect enhancer activation, as inferred from histone H3K27 acetylation, chromatin accessibility and occupancy of Mediator and cohesin. Strikingly, CRISPRa-mediated rescue of enhancer transcription in Spt5-depleted cells restored Igh gene expression. Thus, Spt5-mediated enhancer transcription serves as a direct and causal link between Igh super-enhancer activation and its physical interaction with target promoters.
2020-02-27 | GSE132029 | GEO
Project description:<p>Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with Ectrodactyly Ectodermal Dysplasia Cleft Lip/Palate (EEC) syndrome. Underlying molecular mechanism of these mutations however remain unclear. Here we characterized the transcriptome and epigenome of p63 mutant keratinocytes derived from EEC patients. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed an altered enhancer landscape in p63 mutant keratinocytes contributed by loss of p63-bound active enhancers and by unexpected gain of enhancers. The gained enhancers were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression and the altered enhancer landscape. Our findings identify an unreported disease mechanism whereby mutant p63 rewires the enhancer landscape and affects epidermal cell identity, consolidating the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes.</p>
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Project description:Remote enhancers are thought to interact with their target promoters via physical proximity, yet the importance of this proximity for enhancer function remains unclear. Here, we investigate the 3D conformation of enhancers during mammalian development by generating high-resolution tissue-resolved contact maps for nearly a thousand enhancers with characterized in vivo activities in ten murine embryonic tissues. 61% of developmental enhancers bypass their neighboring genes, which are often marked by promoter CpG methylation. The majority of enhancers display tissue-specific 3D conformations, and both enhancer–promoter and enhancer–enhancer interactions are moderately but consistently increased upon enhancer activation in vivo. Less than 14% of enhancer–promoter interactions form stably across tissues; however, these invariant interactions form in the absence of the enhancer and are likely mediated by adjacent CTCF binding. Our results highlight the general significance of enhancer–promoter physical proximity for developmental gene activation in mammals.
2024-01-03 | GSE217078 | GEO
Project description:Long-range developmental enhancers can regulate cell-type specific target gene expression over distances that exceed hundreds of thousands of base pairs in mammals. Although higher-order chromatin organization provides support for such long-range enhancer—promoter interactions, the genetic factors that regulate these interactions during mammalian development remain largely unexplored. To address this central question, we replaced a limb enhancer, located >800,000 base pairs from its target promoter, with equivalent limb enhancers of similar strength from other genomic loci. We used this replacement strategy to generate six knock-in mouse strains, with enhancers from four distinct genomic loci. All enhancers drove strong expression in developing limb buds when placed adjacent to a reporter gene. However, when transplanted to a distal location, all four enhancers failed to activate remote gene expression and distal limb outgrowth, suggesting that proximally-active enhancers cannot activate transcription remotely. Including a highly conserved, but previously uncharacterized, sequence found adjacent to a long-range limb enhancer rescued gene expression and limb outgrowth. This cis-acting Range EXtender (REX) element does not have classical enhancer activity but is necessary and sufficient for enhancer–promoter communication over very long distances in vivo. The REX element contains highly conserved [C/T]AATTA consensus sequences that match binding preferences of LIM-homeodomain (LHX) transcription factors. We used multiomic single-cell ATAC-seq/RNA-seq profiling to identify [C/T]AATTA homeodomain motifs next to thousands of long-range limb enhancers. The presence of these motifs positively correlates with E–P distance genome-wide. Our data support a model where REX elements facilitate target gene activation by remote enhancers over very long distances in mammalian genomes.
2024-05-28 | GSE243635 | GEO
Project description:We performed the integrative transcriptome analysis of human esophageal squamous cell carcinoma (ESCC) using Illumina high-throughput sequencing. A total of 187 million 38bp sequencing reads were generated containing 7 billion bases for three pairs of matched patient-derived ESCC clinical specimens and their adjacent non-tumorous tissues. By investigating the digital gene expression profiling, we found 1425 genes significantly differentially expressed and detected more than 9000 SNPs across all six samples. We also identified protein tyrosine kinase 6 (PTK6) as a novel tumor suppressor gene, which is critical in ESCC development. Analysis of whole transcriptome from 3 paired patient-derived ESCC clinical specimens and their adjacent non-tumorous tissues.
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