Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enhancer RNA transcriptomics-wide association study reveals an atlas of pan-cancer susceptibility eRNAs

ABSTRACT: Increasing evidence has demonstrated that enhancer RNAs (eRNAs) play essential roles in human diseases. However, the complete identification of disease-related subsets of eRNAs remains a major challenge. Here, we construct an atlas of common and rare genetic variants influencing the expression of enhancer RNAs across 49 human tissues. We identify 11,757 eRNA quantitative trait loci (eRNA-QTLs) associated with the expression of 89.75% annotated eRNAs. Mechanically, eRNA-QTLs frequently altered the binding motifs of transcription factors and were further experimentally validated by CRISPR-based base editing. We also observed that 28.48% of cancer signals were co-localized with eRNA-QTLs. Utilizing our newly developed eRNA transcriptome-wide association study (eRNA-TWAS) model, we have effectively identified 259 cancer susceptibility eRNAs spanning 23 distinct cancer types. Notably, among the identified eRNAs, these eRNA-linked cancer susceptibility genes exhibit significant dependence across various cancer cell lines. Interestingly, cancer risk can be significantly influenced by rare functional variants that are linked to eRNAs with transcriptomic outliers. Additionally, we develop a comprehensive and flexible data portal for exploring the genetic underpinnings of eRNAs. Overall, this study reveals a systematic landscape of genetic dependencies on eRNAs across pan-cancers and significantly expands the pool of disease-associated eRNAs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE242322 | GEO | 2025/02/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Assessing eRNAs associated with a cytokine-sensing mammary super-enhancer

Project description:Enhancers are transcription factor platforms that also bind RNA polymerase II and generate enhancer RNAs (eRNA). Although eRNAs have been suggested as predictors of enhancer activities and possibly key components facilitating transcription, there is little genetic evidence to support this. We address the biology of eRNAs in vivo and investigate eRNA patterns, expression levels and possible functions within a mammary-specific super-enhancer that is composed of three units with distinct transcriptional capacities. We show that eRNA levels do not correspond with the activities of their respective enhancer units. However, changes in eRNA expression upon deletion of individual enhancer units reflect the change in overall super-enhancer activity. These data provide genetic evidence that eRNA levels are not a reliable readout of individual enhancers, but they predict superenhancer activity in the absence of constituent elements.

2018-06-01 | GSE104206 | GEO

Functional Importance of eRNAs for Estrogen-dependent Gene Transcriptional Activation

Project description:The functional importance of gene enhancers in regulated gene expression is well established. In addition to widespread transcription of long non-coding RNA (ncRNA) transcripts in mammalian cells, bidirectional ncRNAs referred to as eRNAs are present on enhancers. However, it has remained unclear whether these eRNAs are functional, or merely a reflection of enhancer activation. Here, we report that 17 ?-estradiol (E2)-bound estrogen receptor alpha (ER?) on enhancers causes a global increase in eRNA transcription on enhancers adjacent to E2 upregulated coding genes. These induced eRNAs, as functional transcripts, appear to exert important roles for the observed ligand-dependent induction of target coding genes, causing an increased strength of specific enhancer:promoter looping initiated by ER? binding. Cohesin, present on many ER?-regulated enhancers even prior to ligand treatment, apparently contributes to E2-dependent gene activation by stabilizing E2/ER?/eRNA-induced enhancer:promoter looping. Our data indicate that eRNAs are likely to exert important functions in many regulated programs of gene transcription. The ChIP-seqs in this study measure the binding landscape of master transcription regulator of estrogen signaling - ER?, together with common histone marks including H3K27ac and H3K4me1 in MCF7 cells. These data serve as the basis to understand the enhancer map and subsequent analysis of eRNA expression using GRO-seq. The GRO-seq measures the trancription of nascent RNAs in the genome. From MCF7 cells treated with veichle or estrodial, we could identify estrogen-regulated eRNAs and subsequently could study their functions.

2013-06-04 | E-GEOD-45822 | biostudies-arrayexpress

eRNAs and super-enhancer lncRNAs are functional in human prostate cancer

Project description:Prostate cancer (PCa) is one of the most commonly diagnosed cancers in males worldwide. lncRNAs (long non-coding RNAs) play a significant role in the occurrence and development of PCa. eRNAs (enhancer RNA) and SE-lncRNAs (super-enhancer lncRNA) are important elements of lncRNAs, but the role of eRNAs and SE-lncRNAs in PCa remains largely unclear. In this work, we identified 681 eRNAs and 292 SE-lncRNAs that were expressed differentially in PCa using a microarray. We constructed a transcriptional regulation network that eRNA related enhancer and the target genes shared the same TF binding motifs. Further, we investigated whether CTCF played a role in mediating the transcriptional regulation network. eRNAs, especially those that regulate androgen response genes, may be candidates for prognostic biomarkers and therapy targets. Our work provide a new perspective for developing medical treatments and therapies for prostate cancer.

2020-10-13 | GSE155056 | GEO

Functional Importance of eRNAs for Estrogen-dependent Gene Transcriptional Activation

2013-06-04 | GSE45822 | GEO

eRNAs Promote Transcription by Establishing Chromatin Accessibility at Defined Genomic Loci

Project description:Transcription factors and DNA regulatory binding motifs are fundamental components of the gene regulatory network (GRN). Here, by using genome-wide occupancy profiling of master regulators of MyoGenesis (MyoD and MyoGenin), we show their extensive occupancy in the extragenic enhancer regions coinciding with RNA synthesis (i.e. eRNA). In particular, multiple regions coding for eRNAs were observed within regulatory region of MYOD1, including previously characterized Distal Regulatory Regions (DRR) and Core Enhancer (CE). While CERNA enhanced RNA polymerase II (PolII) occupancy and transcription at MYOD1, DRRRNA acted in trans to activate the downstream MyoGenic GRN. The deployment of transcriptional machinery to appropriate loci is contingent on chromatin accessibility, a rate-limiting step preceding PolII assembly. By nuclease sensitivity assay, we show that eRNAs increase genomic access to the transcriptional complex at defined regulatory regions. In conclusion, our data suggest eRNAs establish a cell-type-specific transcriptional circuitry by directing chromatin-remodeling events. Examination of MyoD and MyoG binding events and production of RNA at the enhancer sites during myogenic differentiation. We performed RNAi against enhancer-derived RNA (DRRi) which resulted in reduction of chromatin accessiblity and RNA polymerase II occupancy at defined regulatory elements. In complementary experiments, overexpression of DRR-RNA (pHAN_DRR1.2) resulted in early activation of MyoG. GFPi and GFP overexpression (pHAN_GFP) were used as control in these experiments, respectively.

2013-09-15 | E-GEOD-49313 | biostudies-arrayexpress

eRNAs Promote Transcription by Establishing Chromatin Accessibility at Defined Genomic Loci

2013-09-15 | GSE49313 | GEO

Activation of the P-TEFb Complex by Lethal Prostate Cancer-Associated Enhancer RNAs [RNA-Seq]

Project description:Castration resistant prostate cancer (CRPC) is a lethal disease1-4. Aberrant activation of the androgen receptor (AR) becomes a central mechanism contributing to the resistance of endocrine therapies2,3. Here we demonstrate that non-coding RNAs transcribed from the AR bound-enhancers RNAs (AR-eRNAs) are upregulated in human CRPC cells in vitro, xenografts in vivo and patient tissues. Expression of a subset of genes with elevated AR-eRNAs, including TLE1 and HTR3A, is inversely correlated with biochemical recurrence-free survival of CRPC patients. We identify aan HIV-1 TAR-like (TAR-L) motif in AR-eRNAs of AR target genes including KLK3 (or PSA) and TMPRSS2. The TAR-L motif is important for these eRNAs to bind to CYCLIN T1 of the positive transcription elongation factor b (P-TEFb) complex. Knockdown of PSA eRNA diminishes RNA polymerase II (Pol II) serine-2 (Ser-2) phosphorylation at the PSA promoter. The TAR-L motif in KLK3 eRNA is crucial for effective transcription of PSA mRNA. Together, wWe demonstrate a P-TEFb activation function of eRNA and reveal aberrant eRNA expression as a functional indicator of AR abnormality in CRPC. Our results also suggest that eRNAs as amay be a potential target for CRPC therapy. Total RNA sequencing of two prostate cancer cells. Data were generated by deep sequencing, in diplicate, using Illumina HiSeq 2000.

2016-02-12 | E-GEOD-55030 | biostudies-arrayexpress

AxiomM-BM-. Exome 319 Array data to identify susceptible genetic variations of gastric cancer

Project description:To efficiently identify genetic susceptibility variants for gastric cancer, including rare coding variants, we performed an exome chip-based array study. We found that a linkage disequilibrium (LD) block containing 2 significant variants in PSCA gene increased the risk and two blocks that included 15 suggested variants including TRIM31, TRIM 40, TRIM 10, and TRIM26 regions, and included one suggested variant and OR2H2 gene showed protective associations with gastric cancer susceptibility. In addition, the PLEC region (rs200893203), FBLN2 region (rs201192415), and EPHA2 region (rs3754334) were associated with increased susceptibility We performed an exome chip-based array study in 329 gastric cancer cases and 683 controls.

2014-06-11 | E-GEOD-58356 | biostudies-arrayexpress

Activation of the P-TEFb Complex by Lethal Prostate Cancer-Associated Enhancer RNAs [ChIP-Seq]

Project description:Castration resistant prostate cancer (CRPC) is a lethal disease1-4. Aberrant activation of the androgen receptor (AR) becomes a central mechanism contributing to the resistance of endocrine therapies2,3. Here we demonstrate that non-coding RNAs transcribed from the AR bound-enhancers RNAs (AR-eRNAs) are upregulated in human CRPC cells in vitro, xenografts in vivo and patient tissues. Expression of a subset of genes with elevated AR-eRNAs, including TLE1 and HTR3A, is inversely correlated with biochemical recurrence-free survival of CRPC patients. We identify aan HIV-1 TAR-like (TAR-L) motif in AR-eRNAs of AR target genes including KLK3 (or PSA) and TMPRSS2. The TAR-L motif is important for these eRNAs to bind to CYCLIN T1 of the positive transcription elongation factor b (P-TEFb) complex. Knockdown of PSA eRNA diminishes RNA polymerase II (Pol II) serine-2 (Ser-2) phosphorylation at the PSA promoter. The TAR-L motif in KLK3 eRNA is crucial for effective transcription of PSA mRNA. Together, wWe demonstrate a P-TEFb activation function of eRNA and reveal aberrant eRNA expression as a functional indicator of AR abnormality in CRPC. Our results also suggest that eRNAs as amay be a potential target for CRPC therapy. Androgen receptor (AR) binding sites in human prostate cancer cell lines, LNCaP and C4-2, were studied using ChIP-seq. ChIP enriched and input DNA were sequenced using Illumina HiSeq 2000.

2016-02-12 | E-GEOD-55031 | biostudies-arrayexpress

Axiom® Exome 319 Array data to identify susceptible genetic variations of gastric cancer

2014-06-11 | GSE58356 | GEO