Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Massively parallel reporter assays combined with cell-type specific eQTL identified a functional melanoma risk variant in HIV-1 restriction gene, MX2

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE129250 | GEO | 2020/04/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Massively parallel reporter assays combined with cell-type specific eQTL identified a functional melanoma risk variant in HIV-1 restriction gene, MX2 [MX2_overexpress_time]

Project description:Genome-wide association studies (GWAS) have identified twenty melanoma susceptibility loci. To identify susceptibility genes and variants simultaneously from multiple GWAS loci, we integrated massively-parallel reporter assays (MPRA) with melanocyte-specific expression quantitative trait locus (eQTL) profiling. We identified thirty-nine candidate functional variants displaying allelic transcriptional activity, of which nine from four loci were also correlated with local gene expression in melanocytes (CTSS, CASP8, MX2, and MAFF). Among these, we further characterized the locus in MX2 gene on chromosome band Chr21q22.3 and validated a functional variant, rs398206. The functional variant mediates allelic transcriptional activity via binding of the transcription factor, YY1. This allelic transcriptional regulation largely accounts for a significant cis-eQTL of the HIV-1 restriction gene, MX2, in primary melanocytes, where the melanoma risk-associated A allele is correlated with higher MX2 levels. Melanocyte-specific transgenic expression of human MX2 in a zebrafish model demonstrated an accelerated melanoma formation in a BRAFV600E background. Thus, using an efficient scalable approach to streamline GWAS follow-up functional studies, we uncovered a pleiotropic function of MX2 in melanoma susceptibility.

2020-04-23 | GSE149161 | GEO

Massively parallel reporter assays combined with cell-type specific eQTL identified a functional melanoma risk variant in HIV-1 restriction gene, MX2 [MX2_overexpress]

2020-04-20 | GSE129237 | GEO

Massively parallel reporter assays combined with cell-type specific eQTL identified a functional melanoma risk variant in HIV-1 restriction gene, MX2 [MPRA NGS]

2020-04-20 | GSE129242 | GEO

Massively parallel reporter assays of melanoma risk variants identify MX2 as a gene promoting melanoma.

Project description:Genome-wide association studies (GWAS) have identified ~20 melanoma susceptibility loci, most of which are not functionally characterized. Here we report an approach integrating massively-parallel reporter assays (MPRA) with cell-type-specific epigenome and expression quantitative trait loci (eQTL) to identify susceptibility genes/variants from multiple GWAS loci. From 832 high-LD variants, we identify 39 candidate functional variants from 14 loci displaying allelic transcriptional activity, a subset of which corroborates four colocalizing melanocyte cis-eQTL genes. Among these, we further characterize the locus encompassing the HIV-1 restriction gene, MX2 (Chr21q22.3), and validate a functional intronic variant, rs398206. rs398206 mediates the binding of the transcription factor, YY1, to increase MX2 levels, consistent with the cis-eQTL of MX2 in primary human melanocytes. Melanocyte-specific expression of human MX2 in a zebrafish model demonstrates accelerated melanoma formation in a BRAFV600E background. Our integrative approach streamlines GWAS follow-up studies and highlights a pleiotropic function of MX2 in melanoma susceptibility.

| S-EPMC7264232 | biostudies-literature

Massively parallel reporter assays combined with cell-type specific eQTL identified a functional melanoma risk variant in HIV-1 restriction gene, MX2

Project description:Massively parallel reporter assays combined with cell-type specific eQTL identified a functional melanoma risk variant in HIV-1 restriction gene, MX2

| PRJNA530602 | ENA

Transcriptional-regulatory convergence across functional MDD risk variants identified by massively parallel reporter assays.

Project description:Family and population studies indicate clear heritability of major depressive disorder (MDD), though its underlying biology remains unclear. The majority of single-nucleotide polymorphism (SNP) linkage blocks associated with MDD by genome-wide association studies (GWASes) are believed to alter transcriptional regulators (e.g., enhancers, promoters) based on enrichment of marks correlated with these functions. A key to understanding MDD pathophysiology will be elucidation of which SNPs are functional and how such functional variants biologically converge to elicit the disease. Furthermore, retinoids can elicit MDD in patients and promote depressive-like behaviors in rodent models, acting via a regulatory system of retinoid receptor transcription factors (TFs). We therefore sought to simultaneously identify functional genetic variants and assess retinoid pathway regulation of MDD risk loci. Using Massively Parallel Reporter Assays (MPRAs), we functionally screened over 1000 SNPs prioritized from 39 neuropsychiatric trait/disease GWAS loci, selecting SNPs based on overlap with predicted regulatory features-including expression quantitative trait loci (eQTL) and histone marks-from human brains and cell cultures. We identified >100 SNPs with allelic effects on expression in a retinoid-responsive model system. Functional SNPs were enriched for binding sequences of retinoic acid-receptive transcription factors (TFs), with additional allelic differences unmasked by treatment with all-trans retinoic acid (ATRA). Finally, motifs overrepresented across functional SNPs corresponded to TFs highly specific to serotonergic neurons, suggesting an in vivo site of action. Our application of MPRAs to screen MDD-associated SNPs suggests a shared transcriptional-regulatory program across loci, a component of which is unmasked by retinoids.

| S-EPMC8298436 | biostudies-literature

Massively parallel reporter assays combined with cell-type specific eQTL identified a functional melanoma risk variant in HIV-1 restriction gene, MX2 [MX2_overexpress]

Project description:Massively parallel reporter assays combined with cell-type specific eQTL identified a functional melanoma risk variant in HIV-1 restriction gene, MX2 [MX2_overexpress]

| PRJNA530569 | ENA

Massively parallel reporter assays combined with cell-type specific eQTL identified a functional melanoma risk variant in HIV-1 restriction gene, MX2 [MX2_overexpress_time]

Project description:Massively parallel reporter assays combined with cell-type specific eQTL identified a functional melanoma risk variant in HIV-1 restriction gene, MX2 [MX2_overexpress_time]

| PRJNA627482 | ENA

MPRAnalyze: statistical framework for massively parallel reporter assays.

Project description:Massively parallel reporter assays (MPRAs) can measure the regulatory function of thousands of DNA sequences in a single experiment. Despite growing popularity, MPRA studies are limited by a lack of a unified framework for analyzing the resulting data. Here we present MPRAnalyze: a statistical framework for analyzing MPRA count data. Our model leverages the unique structure of MPRA data to quantify the function of regulatory sequences, compare sequences' activity across different conditions, and provide necessary flexibility in an evolving field. We demonstrate the accuracy and applicability of MPRAnalyze on simulated and published data and compare it with existing methods.

| S-EPMC6717970 | biostudies-literature

Massively parallel reporter assays combined with cell-type specific eQTL identified a functional melanoma risk variant in HIV-1 restriction gene, MX2 [MPRA NGS]

Project description:Massively parallel reporter assays combined with cell-type specific eQTL identified a functional melanoma risk variant in HIV-1 restriction gene, MX2 [MPRA NGS]

| PRJNA530577 | ENA

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