Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genetic neuroscience: How human genes and alleles shape neuronal phenotypes

ABSTRACT: Genetic neuroscience: How human genes and alleles shape neuronal phenotypes

PROVIDER: PRJNA633306 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Genetic neuroscience: How human genes and alleles shape neuronal phenotypes

Project description:Genetic neuroscience: How human genes and alleles shape neuronal phenotypes

| PRJNA633307 | ENA

Major alleles of CDCA7α shape CG-methylation in Arabidopsis thaliana

Project description:Major alleles of CDCA7α shape CG-methylation in Arabidopsis thaliana

| PRJNA1197390 | ENA

Major alleles of CDCA7α shape CG-methylation in Arabidopsis thaliana [WGBS]

Project description:Major alleles of CDCA7α shape CG-methylation in Arabidopsis thaliana [WGBS]

| PRJNA1196491 | ENA

Major alleles of CDCA7α shape CG-methylation in Arabidopsis thaliana [RNA-seq]

Project description:Major alleles of CDCA7α shape CG-methylation in Arabidopsis thaliana [RNA-seq]

| PRJNA1196944 | ENA

Major alleles of CDCA7α shape CG-methylation in Arabidopsis thaliana [ChIP-Seq]

Project description:Major alleles of CDCA7α shape CG-methylation in Arabidopsis thaliana [ChIP-Seq]

| PRJNA1196495 | ENA

Proteasomal activation ameliorates neuronal phenotypes linked to FBXO11-deficiency [human]

Project description:Proteasomal activation ameliorates neuronal phenotypes linked to FBXO11-deficiency [human]

| PRJNA1213861 | ENA

Proteasomal activation ameliorates neuronal phenotypes linked to FBXO11-deficiency [fly]

Project description:Proteasomal activation ameliorates neuronal phenotypes linked to FBXO11-deficiency [fly]

| PRJNA1213860 | ENA

Proteasomal activation ameliorates neuronal phenotypes linked to FBXO11-deficiency [human]

Project description:Haploinsufficiency of FBXO11, encoding a ubiquitin ligase complex subunit, is associated with a variable neurodevelopmental disorder. So far, the underlying nervous-system related pathomechanisms are poorly understood, and specific therapies are lacking. Using a combined approach, we established an FBXO11-deficient human stem cell-based neuronal model using CRISPR/CAS9 and a Drosophila model using tissue specific knockdown techniques. We performed transcriptomic analyses on iPSC-derived neurons and molecular phenotyping in both models. RNA-sequencing revealed disrupted transcriptional networks related to processes important for neuronal development, such as differentiation, migration and cell signaling. Consistently, we found that loss of FBXO11 leads to neuronal phenotypes such as impaired neuronal migration and abnormal proliferation/differentiation balance in human cultured neurons and impaired dendritic development and behavior in Drosophila. Interestingly, application of three different proteasome activating substances could alleviate FBXO11-deficiency-associated phenotypes in both human neurons and flies. One of these substances is the long-approved drug Verapamil, opening the possibility of drug repurposing in the future. Our study shows the importance of FBXO11 for neurodevelopment and highlights the reversibility of related phenotypes, opening an avenue for potential development of therapeutic approaches through drug repurposing.

2025-03-25 | GSE287638 | GEO

Proteasomal activation ameliorates neuronal phenotypes linked to FBXO11-deficiency [fly]

2025-03-25 | GSE287637 | GEO

Major alleles of CDCA7α shape CG-methylation in Arabidopsis thaliana

Project description:DNA methylation is a key epigenetic mark that impacts gene expression and represses transposable elements (TEs) in eukaryotes. Numerous examples of cis-elements targeted by DNA methylation, particularly at CG sites (mCG), have been reported to be under selective pressure in animals and plants. By contrast, there is limited knowledge of trans-regulators of mCG leading to adaptation. Here, using genome-wide association studies, we identify CELL DIVISION CYCLE-ASSOCIATED PROTEIN 7 ALPHA (CDCA7α) as a trans-regulator of mCG in natural populations of Arabidopsis thaliana. CDCA7α and its paralog, CDCA7β, directly bind to the chromatin remodeler DECREASE IN DNA METHYLATION 1 (DDM1), which facilitates access of methyltransferases to DNA. CDCA7α/β selectively regulates mCG and minimally impacts other DDM1-dependent processes such as non-CG methylation and histone variant deposition. We identify the cis-regulatory sequence modulating CDCA7α expression in natural populations and determining the degree of mCG and TE silencing. The geographic distribution of CDCA7α alleles suggests that new alleles have repeatedly expanded to novel ecological niches, indicating a potential role in local adaptation. Altogether, our findings provide new insight into how changes in global DNA methylation levels through transcriptional regulation of the epigenetic machinery have the capacity to facilitate local adaptation.

2025-01-13 | GSE284119 | 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