Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Characterization of GJB2 cis-regulatory elements in the DFNB1 locus

ABSTRACT: Although most disease-causing variants are within coding region of genes, it is now well established that cis-acting regulatory sequences, depending on 3D-chromatin organization, are required for temporal and spatial control of gene expression. Disruptions of such regulatory elements and/or chromatin conformation are likely to play a critical role in human genetic disease. Hence, recurrent monoallelic cases of the most common hereditary type of nonsyndromic hearing loss (i.e. DFNB1) carrying out only one identified pathogenic allele, led to strongly suggest the presence of uncharacterized distal cis-acting elements in the missing allele. Herewith, we study the spatial organization of a large DFNB1 locus encompassing the gap junction protein beta 2 (GJB2) gene, the most frequently mutated gene in this inherited hearing loss, with the chromosome conformation capture carbon copy technology (5C). By combining this approach with functional activity reporter assays and mapping of CCCTC-binding factor (CTCF) along the DFNB1 locus by quantitative real-time PCR chromatin immunoprecipitation, we identify a novel set of cooperating GJB2 cis-acting elements and propose a DFNB1 three-dimensional looping regulation model. A loop chromatin forming, allows bringing closer enhancers to the GJB2 promoter, but also avoids GJB2 silencing with an enhancer-blocking insulator activity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE128881 | GEO | 2020/03/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

3D chromatin organization involving MEIS1 factor in the cis-regulatory landscape of GJB2

Project description:To study GJB2 gene regulation, we used Circular Chromosome Conformation Capture technique (4C) to analyse chromatin interactions inside DFNB1 locus.

2022-07-13 | GSE201205 | GEO

The pathogenesis of common Gjb2 mutation associated with human hereditary deafness in mice

Project description:Mutations in GJB2 (Gap junction protein beta 2) are the most common genetic cause of non-syndromic hereditary deafness in humans, especially the 35delG and 235delC mutations. Owing to the homozygous-lethal of Gjb2 mutation in mice, there are currently no perfect mouse models carrying Gjb2 mutation to mimic human hereditary deafness and unveil the pathogenesis. Here, we first constructed heterozygous mutant mice, Gjb2+/35delG and Gjb2+/235delC, through androgenic haploid embryonic stem cells (AG-haESCs) mediated semi-cloning technology, which showed normal hearing function at P28. Furthermore, a homozygous mutant mouse model, Gjb235delG/35delG, was generated via enhanced tetraploid embryo complementation, which exhibited profound hearing loss like human patients at P14. Mechanism analysis showed that Gjb2 35delG disrupts the formation of intercellular gap junction channel and tunnel of Corti, and hair cell mechanotransduction, rather than the development of hair cells. Collectively, our study provides ideal mouse models for understanding the pathogenic mechanism and opens up a new avenue for investigating the treatment for DFNB1A-related hereditary deafness.

2023-05-12 | GSE215106 | GEO

Characterization of GJB2 cis-regulatory elements in the DFNB1 locus

Project description:Characterization of GJB2 cis-regulatory elements in the DFNB1 locus

| PRJNA529209 | ENA

3D chromatin organization involving MEIS1 factor in the cis-regulatory landscape of GJB2

Project description:3D chromatin organization involving MEIS1 factor in the cis-regulatory landscape of GJB2

| PRJNA830351 | ENA

Gene expression and functional analysis of GJB2 mutated HaCaT cell lines [G130V]

Project description:Vohwinkel syndrome, VS (OMIM#124500), a rare autosomal dominant genetic disease, with less than 50 reported cases in the literature. Although clinical symptoms of VS are complex, which are caused by GJB2 mutation is more typical. To explore related differential genes and signaling pathways of Vohwinkel syndrome (VS) caused by mutations of GJB2. Human Gene Expression Array of the GJB2-VS mutated (G130V) HaCaT cell lines and identified distinct classes of up- and down- regulated genes during this process.

2023-09-30 | GSE200384 | GEO

Gene expression and functional analysis of GJB2 mutated HaCaT cell lines [D66H]

Project description:Vohwinkel syndrome, VS (OMIM#124500), a rare autosomal dominant genetic disease, with less than 50 reported cases in the literature. Although clinical symptoms of VS are complex, which are caused by GJB2 mutation is more typical. To explore related differential genes and signaling pathways of Vohwinkel syndrome (VS) caused by mutations of GJB2. Human Gene Expression Array of two types of GJB2-VS mutated (G130V and D66H) HaCaT cell lines and identified distinct classes of up- and down- regulated genes during this process.

2023-09-30 | GSE200386 | GEO

NOMe-HiC: joint profiling of genetic variants, DNA methylation, chromatin accessibility, and 3D genome in the same DNA molecule

Project description:Cis-regulatory elements coordinate the regulation of their targeted genes’ expression. However, the joint measurement of cis-regulatory elements’ activities and their interactions in spatial proximity is limited by the current sequencing approaches. We describe a method, NOMe-HiC, which simultaneously captures single nucleotide polymorphisms, DNA methylation, chromatin accessibility (GpC methyltransferase footprints), and chromosome conformation changes from the same DNA molecule, together with the transcriptome, in a single assay. NOMe-HiC shows high concordance with state-of-the-art mono-omic assays across different molecular measurements and reveals coordinated chromatin accessibility at distal genomic segments in spatial proximity and novel types of long-range allele-specific chromatin accessibility.

2023-02-28 | GSE189158 | GEO

RNA-seq of human glioblastoma (GBM) cell lines treated with shRNA against GJB2, SCN9A, or non-targeted controls

Project description:Ion channels and related proteins of the ion permeome (IP) are common drug targets; however, their roles in cancer remain understudied. We performed a computational, pan-cancer analysis of druggable IP genes to prioritise targets for therapeutic and biomarker development. Two candidate biomarkers in glioblastoma (GBM), GJB2 and SCN9A, associated with poor prognosis in multiple datasets, as well as inter- and intratumoral heterogeneity and malignant cell types. We used shRNA to knock down GJB2 (G5) and SCN9A (S3) in patient-derived GBM cells (729) in triplicates and performed whole transcriptome sequencing to profile the transcriptome-wide changes. Pathway enrichment identified neural projection and proliferation pathways were significantly dysregulated in GJB2 and SCN9A GBM cell line knockdowns compared to non-targeted shRNA controls (Scr). Our study underlines altered bioelectrical signalling as a cancer hallmark and provides a catalogue of IP genes for functional experiments and therapy development.

2023-09-29 | E-MTAB-12859 | biostudies-arrayexpress

Comprehensive, high resolution analysis of cis-acting regulatory networks at the alpha globin locus (HTS)

Project description:We have combined the 4C chromosome conformation capture protocol with high throughput, genome-wide sequence analysis to characterise in full a cis-acting regulatory network at a single locus. In contrast to methods which identify large interacting regions (10-1000kb), the 4C approach provides a comprehensive, high resolution analysis of a specific locus with the aim of defining, in detail, all cis- regulatory elements controlling a single gene or gene cluster. Using the human M-NM-1-globin locus as a model we detected all known local and long-range interactions with this gene cluster. In addition we identified two interactions with genes located 300 kb (NME4) and 625 kb (FAM173a) from the M-NM-1-globin cluster. Using paired-end sequencing it was possible for the first time to identify interactions between specific subsets of cis-regulatory elements in populations of cells and within individual cells. Two biological replicates of 4C amplification from the promoters of the human HBA gene promoters. Sequenced as paired end fragments usinig Illumina GAII

2013-06-06 | E-GEOD-42382 | biostudies-arrayexpress

Identification of lineage-specific cis-regulatory modules associated with variation in transcription factor binding and chromatin activity using Ornstein-Uhlenbeck models

Project description:Whole-chromatin profile (FAIRE-seq) in three Drosophila species (D. melanogaster, D. pseudoobscura and D. virilis) in eye-antennal imaginal discs at the stage of third instar wandering larvae. By the use of Ornstein-Uhlenbeck methods, we assess the evolutionary forces acting on regulatory elements (cis-level) on chromatin activity across Drosophila eye-antennal imaginal discs at the stage of third instar larvae.

2015-06-17 | E-GEOD-59706 | biostudies-arrayexpress

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