Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CASCADE - Customizable high-throughput platform for profiling cofactor recruitment to DNA to characterize cis-regulatory elements and screen non-coding SNPs

ABSTRACT: Determining how DNA variants affect the binding of regulatory complexes to cis-regulatory elements (CREs) and non-coding single-nucleotide polymorphisms (ncSNPs) is a challenge in genomics. To address this challenge, we present CASCADE (Comprehensive ASsessment of Complex Assembly at DNA Elements) – a protein-binding microarray (PBM)-based approach to profile the recruitment of cofactors (COFs) to DNA sequence variants, and to infer the identity of the transcription factor-cofactor (TF-COF) complexes involved. We use CASCADE to characterize regulatory complexes binding to CREs and SNP quantitative trait loci (SNP-QTLs) in resting and stimulated human macrophages. By profiling p300 we correctly identify IRF3 and NF-κB as LPS-dependent regulators of the chemokine CXCL10, and by profiling a set of five functionally diverse COFs we identify a prevalence of ETS sites mediating COF recruitment at SNP-QTLs in macrophages. Our results demonstrate that CASCADE is a customizable, high-throughput platform to link DNA variants with the biophysical complexes that mediate functions such as chromatin modification or remodeling in a cell state-specific manner.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148945 | GEO | 2020/04/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hybrid mice reveal parent-of-origin and cis- and trans-regulatory effects in the retina

Project description:A fundamental challenge in genomics is to map DNA sequence variants onto changes in gene expression. Gene expression is regulated by cis-regulatory elements (CREs, i.e., enhancers, promoters, and silencers) and the trans factors (e.g., transcription factors) that act upon them. A powerful approach to dissecting cis and trans effects is to compare F1 hybrids with F0 homozygotes. Using this approach and taking advantage of the high frequency of polymorphisms in wild-derived inbred Cast/EiJ mice relative to the reference strain C57BL/6J, we conducted allele-specific mRNA-seq analysis in the adult mouse retina, a disease-relevant neural tissue. We found that cis effects account for the bulk of gene regulatory divergence in the retina. Many CREs contained functional (i.e., activating or silencing) cis-regulatory variants mapping onto altered expression of genes, including genes associated with retinal disease. By comparing our retinal data with previously published liver data, we found that most of the cis effects identified were tissue-specific. Lastly, by comparing reciprocal F1 hybrids, we identified evidence of imprinting in the retina for the first time. Our study provides a framework and resource for mapping cis-regulatory variants onto changes in gene expression, and underscores the importance of studying cis-regulatory variants in the context of retinal disease. Retinas from four classes of 8 week old male mice were collected: F0 C57BL/6J (B6), F0 Cast/EiJ (Cast), F1 B6xCast, and F1 CastxB6. Three replicates per class were generated. Each replicate consisted of a pool of 6-8 retinas. The mRNA-seq was conducted with paired-end 2x101 sequencing on the Illumina HiSeq 2000 platform. One lane of sequencing was run for all twelve samples. An additional lane of sequencing was run for the six F1 samples.

2014-09-01 | E-GEOD-60545 | biostudies-arrayexpress

Open chromatin profiling of human postmortem brain infers functional roles for non-coding schizophrenia loci

Project description:Open chromatin provides access to DNA binding proteins for the correct spatiotemporal regulation of gene expression. Mapping chromatin accessibility has been widely used to identify the location of cis regulatory elements (CREs) including promoters and enhancers. CREs show tissue- and cell-type specificity and disease-associated variants are often enriched for CREs in the tissues and cells that pertain to a given disease. To better understand the role of CREs in neuropsychiatric disorders we applied the Assay for Transposase Accessible Chromatin followed by sequencing (ATAC-seq) to neuronal and non-neuronal nuclei isolated from frozen postmortem human brain by fluorescence-activated nuclear sorting (FANS). Most of the identified open chromatin regions (OCRs) are differentially accessible between neurons and non-neurons, and show enrichment with known cell type markers, promoters and enhancers. Relative to those of non-neurons, neuronal OCRs are more evolutionarily conserved and are enriched in distal regulatory elements. Transcription factor (TF) footprinting analysis identifies differences in the regulome between neuronal and non-neuronal cells and ascribes putative functional roles to a number of non-coding schizophrenia (SCZ) risk variants. Among the identified variants is a Single Nucleotide Polymorphism (SNP) proximal to the gene encoding SNX19. In vitro experiments reveal that this SNP leads to an increase in transcriptional activity. As elevated expression of SNX19 has been associated with SCZ, our data provides evidence that the identified SNP contributes to disease. These results represent the first analysis of OCRs and TF binding sites in distinct populations of postmortem human brain cells and further our understanding of the regulome and the impact of neuropsychiatric disease-associated genetic risk variants.

2017-03-25 | GSE83345 | GEO

Rapid profiling of transcription factor-cofactor interaction networks reveals principles of epigenetic regulation (microarray)

Project description:Transcription factor (TF)-cofactor (COF) interactions define dynamic, cell-specific networks that govern gene expression; however, these networks are understudied due to a lack of methods for high-throughput profiling of DNA-bound TF-COF complexes. Here we describe the Cofactor Recruitment (CoRec) method for rapid profiling of cell-specific TF-COF complexes. We define a lysine acetyltransferase (KAT)-TF network in resting and stimulated T cells. We find promiscuous recruitment of KATs for many TFs and that 35% of KAT-TF interactions are condition specific. KAT-TF interactions identify NF-κB as a primary regulator of acutely induced H3K27ac. Finally, we find that heterotypic clustering of CBP/P300-recruiting TFs is a strong predictor of total promoter H3K27ac. Our data supports clustering of TF sites that broadly recruit KATs as a mechanism for widespread co-occurring histone acetylation marks. CoRec can be readily applied to different cell systems and provides a powerful approach to define TF-COF networks impacting chromatin state and gene regulation.

2024-06-30 | GSE266126 | GEO

Rapid profiling of transcription factor-cofactor interaction networks reveals principles of epigenetic regulation (ChIP-Seq)

2024-06-30 | GSE266125 | GEO

Hybrid mice reveal parent-of-origin and cis- and trans-regulatory effects in the retina

2014-09-01 | GSE60545 | GEO

CRISPRi screen of prostate cancer associated risk cis-regulatory elements [RNA-seq]

Project description:Prostate cancer (PCa) associated risk SNPs are enriched in cis-regulatory elements (CREs). In this study, we screened 260 CREs that contain at least one PCa risk SNP for essentiality in V16A, 22Rv1 and A549 cells. We tiled the CREs and 14 control regions using 5,873 sgRNAs.

2020-12-16 | GSE142809 | GEO

CRISPRi screen of prostate cancer associated risk cis-regulatory elements [ChIP-seq]

2020-12-16 | GSE142810 | GEO

CRISPRi screen of prostate cancer associated risk cis-regulatory elements [Hi-C]

2020-12-16 | GSE143370 | GEO

CRISPRi screen of prostate cancer associated risk cis-regulatory elements [CRISPRi]

2020-12-16 | GSE142808 | GEO

ATAC-seq analysis of K562, MKPL-1, MV4-11, NB4 and U937 leukemia cell lines

Project description:Mutations in protein-coding genes are well established as the basis for human cancer, yet it remains elusive how alterations within non-coding genome, a substantial fraction of which contain cis-regulatory elements (CREs), contribute to cancer pathophysiology. Here we developed an integrative approach to systematically identify and characterize non-coding regulatory variants with functional consequences in human hematopoietic malignancies. Combining targeted resequencing of hematopoietic lineage-specific CREs and mutation discovery, and uncovered 1,837 recurrently mutated CREs containing leukemia-associated non-coding variants. By enhanced CRISPR/dCas9-based CRE perturbation screening and functional analyses, we identified 218 variant-associated oncogenic or tumor suppressive CREs in human leukemia. Non-coding variants at KRAS and PER2 enhancers reside in nuclear receptor (NR) binding regions and modulate transcriptional activities in response to NR signaling in situ in leukemia cells. NR binding sites frequently co-localize with non-coding variants across cancer types. Hence, recurrent non-coding variants connect enhancer dysregulation with nuclear receptor signaling in hematopoietic malignancies.

2020-04-22 | GSE137647 | 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