Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A High-Resolution Map of Human Enhancer RNA Loci Characterizes Super-enhancer Activities in Cancer.

ABSTRACT: Although enhancers play critical roles in cancer, quantifying enhancer activities in clinical samples remains challenging, especially for super-enhancers. Enhancer activities can be inferred from enhancer RNA (eRNA) signals, which requires enhancer transcription loci definition. Only a small proportion of human eRNA loci has been precisely identified, limiting investigations of enhancer-mediated oncogenic mechanisms. Here, we characterize super-enhancer regions using aggregated RNA sequencing (RNA-seq) data from large cohorts. Super-enhancers usually contain discrete loci featuring sharp eRNA expression peaks. We identify >300,000 eRNA loci in ∼377 Mb super-enhancer regions that are regulated by evolutionarily conserved, well-positioned nucleosomes and are frequently dysregulated in cancer. The eRNAs provide explanatory power for cancer phenotypes beyond that provided by mRNA expression through resolving intratumoral heterogeneity with enhancer cell-type specificity. Our study provides a high-resolution map of eRNA loci through which super-enhancer activities can be quantified by RNA-seq and a user-friendly data portal, enabling a broad range of biomedical investigations.

SUBMITTER: Chen H

PROVIDER: S-EPMC7658066 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

A high-resolution landscape of mutations in the <i>BCL6</i> super-enhancer in normal human B cells.

Project description:The super-enhancers (SEs) of lineage-specific genes in B cells are off-target sites of somatic hypermutation. However, the inability to detect sufficient numbers of mutations in normal human B cells has precluded the generation of a high-resolution mutational landscape of SEs. Here we captured and sequenced 12 B cell SEs at single-nucleotide resolution from 10 healthy individuals across diverse ethnicities. We detected a total of approximately 9,000 subclonal mutations (allele frequencies <0.1%); of these, approximately 8,000 are present in the BCL6 SE alone. Within the BCL6 SE, we identified 3 regions of clustered mutations in which the mutation frequency is ∼7 × 10-4 Mutational spectra show a predominance of C > T/G > A and A > G/T > C substitutions, consistent with the activities of activation-induced-cytidine deaminase (AID) and the A-T mutator, DNA polymerase η, respectively, in mutagenesis in normal B cells. Analyses of mutational signatures further corroborate the participation of these factors in this process. Single base substitution signatures SBS85, SBS37, and SBS39 were found in the BCL6 SE. While SBS85 is a denoted signature of AID in lymphoid cells, the etiologies of SBS37 and SBS39 are unknown. Our analysis suggests the contribution of error-prone DNA polymerases to the latter signatures. The high-resolution mutation landscape has enabled accurate profiling of subclonal mutations in B cell SEs in normal individuals. By virtue of the fact that subclonal SE mutations are clonally expanded in B cell lymphomas, our studies also offer the potential for early detection of neoplastic alterations.

| S-EPMC6900602 | biostudies-literature

High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci.

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-09-09 | GSE202474 | GEO

A super-resolution map of the vertebrate kinetochore.

Project description:A longstanding question in centromere biology has been the organization of CENP-A-containing chromatin and its implications for kinetochore assembly. Here, we have combined genetic manipulations with deconvolution and super-resolution fluorescence microscopy for a detailed structural analysis of chicken kinetochores. Using fluorescence microscopy with subdiffraction spatial resolution and single molecule sensitivity to map protein localization in kinetochore chromatin unfolded by exposure to a low salt buffer, we observed robust amounts of H3K9me3, but only low levels of H3K4me2, between CENP-A subdomains in unfolded interphase prekinetochores. Constitutive centromere-associated network proteins CENP-C and CENP-H localize within CENP-A-rich subdomains (presumably on H3-containing nucleosomes) whereas CENP-T localizes in interspersed H3-rich blocks. Although interphase prekinetochores are relatively more resistant to unfolding than sur-rounding pericentromeric heterochromatin, mitotic kinetochores are significantly more stable, reflecting mitotic kinetochore maturation. Loss of CENP-H, CENP-N, or CENP-W had little or no effect on the unfolding of mitotic kinetochores. However, loss of CENP-C caused mitotic kinetochores to unfold to the same extent as their interphase counterparts. Based on our results we propose a new model for inner centromeric chromatin architecture in which chromatin is folded as a layered boustrophedon, with planar sinusoids containing interspersed CENP-A-rich and H3-rich subdomains oriented toward the outer kinetochore. In mitosis, a CENP-C-dependent mechanism crosslinks CENP-A blocks of different layers together, conferring extra stability to the kinetochore.

| S-EPMC2890832 | biostudies-other

High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci [Cut&Run]

Project description:Chromatin organization and enhancer-promoter contacts are critical for establishing unique spatiotemporal gene expression patterns in distinct cell types. Non-coding genetic variants can influence cellular phenotypes by modifying higher-order transcriptional hubs and consequently gene expression. To elucidate transcriptional regulation by non-coding genome in human retina, we mapped chromatin contacts at high resolution and integrated this data with histone marks and super-enhancers (SEs). Retinal SEs exhibited abundant local interactions and reside in topologically associated domains (TADs) with weak boundary insulation. Notably, intra-TAD positioning of SEs correlated with the biological function of their target genes in the retina. We also identified regulatory landscapes of retinopathy genes and uncovered candidate genes for risk variants associated with age-related macular degeneration and glaucoma. Our studies of high-resolution genomic architecture of the human retina provide new insights into genetic control of tissue-specific functions, suggest paradigms for missing heritability, and enable the dissection of multifactorial disease phenotypes.

2022-09-09 | GSE202473 | GEO

High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci [ATAC-seq]

2022-09-09 | GSE202472 | GEO

High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci [Hi-C]

2022-09-09 | GSE202471 | GEO

Identification of cell states using super-enhancer RNA.

Project description:BackgroundA new class of regulatory elements called super-enhancers, comprised of multiple neighboring enhancers, have recently been reported to be the key transcriptional drivers of cellular, developmental, and disease states.ResultsHere, we defined super-enhancer RNAs as highly expressed enhancer RNAs that are transcribed from a cluster of localized genomic regions. Using the cap analysis of gene expression sequencing data from FANTOM5, we systematically explored the enhancer and messenger RNA landscapes in hundreds of different cell types in response to various environments. Applying non-negative matrix factorization (NMF) to super-enhancer RNA profiles, we found that different cell types were well classified. In addition, through the NMF of individual time-course profiles from a single cell-type, super-enhancer RNAs were clustered into several states with progressive patterns. We further investigated the enriched biological functions of the proximal genes involved in each pattern, and found that they were associated with the corresponding developmental process.ConclusionsThe proposed super-enhancer RNAs can act as a good alternative, without the complicated measurement of histone modifications, for identifying important regulatory elements of cell type specification and identifying dynamic cell states.

| S-EPMC8564956 | biostudies-literature

SEdb: a comprehensive human super-enhancer database.

Project description:Super-enhancers are important for controlling and defining the expression of cell-specific genes. With research on human disease and biological processes, human H3K27ac ChIP-seq datasets are accumulating rapidly, creating the urgent need to collect and process these data comprehensively and efficiently. More importantly, many studies showed that super-enhancer-associated single nucleotide polymorphisms (SNPs) and transcription factors (TFs) strongly influence human disease and biological processes. Here, we developed a comprehensive human super-enhancer database (SEdb, http://www.licpathway.net/sedb) that aimed to provide a large number of available resources on human super-enhancers. The database was annotated with potential functions of super-enhancers in the gene regulation. The current version of SEdb documented a total of 331 601 super-enhancers from 542 samples. Especially, unlike existing super-enhancer databases, we manually curated and classified 410 available H3K27ac samples from >2000 ChIP-seq samples from NCBI GEO/SRA. Furthermore, SEdb provides detailed genetic and epigenetic annotation information on super-enhancers. Information includes common SNPs, motif changes, expression quantitative trait locus (eQTL), risk SNPs, transcription factor binding sites (TFBSs), CRISPR/Cas9 target sites and Dnase I hypersensitivity sites (DHSs) for in-depth analyses of super-enhancers. SEdb will help elucidate super-enhancer-related functions and find potential biological effects.

| S-EPMC6323980 | biostudies-literature

High-density volumetric super-resolution microscopy.

Project description:Volumetric super-resolution microscopy typically encodes the 3D position of single-molecule fluorescence into a 2D image by changing the shape of the point spread function (PSF) as a function of depth. However, the resulting large and complex PSF spatial footprints reduce biological throughput and applicability by requiring lower labeling densities to avoid overlapping fluorescent signals. We quantitatively compare the density dependence of single-molecule light field microscopy (SMLFM) to other 3D PSFs (astigmatism, double helix and tetrapod) showing that SMLFM enables an order-of-magnitude speed improvement compared to the double helix PSF by resolving overlapping emitters through parallax. We demonstrate this optical robustness experimentally with high accuracy ( > 99.2 ± 0.1%, 0.1 locs μm-2) and sensitivity ( > 86.6 ± 0.9%, 0.1 locs μm-2) through whole-cell (scan-free) imaging and tracking of single membrane proteins in live primary B cells. We also exemplify high-density volumetric imaging (0.15 locs μm-2) in dense cytosolic tubulin datasets.

| S-EPMC10908787 | biostudies-literature

LSD1 inhibition disrupts super-enhancer activities in CRPC [RNA-seq]

Project description:Our studies revealed a novel oncogenic function of LSD1 in driving PCa progression by activating MYC signaling and mediating CRPC SEs activities, cotargeting LSD1 and BRD4 achieved significant synergistic effects in repressing CRPC tumor growth

2023-06-01 | GSE209887 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data