Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression profile for Gpt2 WT and Gpt2 KO mouse brain tissues with vehicle or dm-αKG treatment

ABSTRACT: Alpha-ketoglutarate (αKG) is required for chromatin demethylation but mechanisms controlling αKG abundance in the nucleus are poorly defined. We designed a biosensor to monitor this metabolite pool in human cells using an αKG-responsive cyanobacterial transcription factor, NtcA, and used it to identify genes that regulate αKG in the nucleus. We defined an inter-organelle pathway in which sequential mitochondrial activities of the GPT2 transaminase and SLC25A11 transporter supply nuclear αKG. In a mouse model of GPT2 Deficiency, an inborn error of metabolism, Gpt2 loss caused histone hypermethylation in the brain and dysregulated neurodevelopmental genes. Restoring αKG counteracted these changes and promoted mouse fitness. Our work provides a tool to directly monitor nuclear αKG and reveals nuclear αKG deficiency as a key pathogenic mechanism underlying GPT2 Deficiency.

ORGANISM(S): Mus musculus

PROVIDER: GSE325502 | GEO | 2026/08/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Histone methylation in Gpt2 KO and Gpt2 WT mouse brain tissues

Project description:Alpha-ketoglutarate (αKG) is required for chromatin demethylation but mechanisms controlling αKG abundance in the nucleus are poorly defined. We designed a biosensor to monitor this metabolite pool in human cells using an αKG-responsive cyanobacterial transcription factor, NtcA, and used it to identify genes that regulate αKG in the nucleus. We defined an inter-organelle pathway in which sequential mitochondrial activities of the GPT2 transaminase and SLC25A11 transporter supply nuclear αKG. In a mouse model of GPT2 Deficiency, an inborn error of metabolism, Gpt2 loss caused histone hypermethylation in the brain and dysregulated neurodevelopmental genes. Restoring αKG counteracted these changes and promoted mouse fitness. Our work provides a tool to directly monitor nuclear αKG and reveals nuclear αKG deficiency as a key pathogenic mechanism underlying GPT2 Deficiency.

2026-08-01 | GSE325503 | GEO

Gene expression profile for Gpt2 WT and Gpt2 KO mouse brain tissues with vehicle or dm-αKG treatment

Project description:Gene expression profile for Gpt2 WT and Gpt2 KO mouse brain tissues with vehicle or dm-αKG treatment

| PRJNA1440359 | ENA

αKG-driven RNA polymerase II transcription of cyclin D1 licenses malic enzyme 2 to promote cell cycle progression

Project description:Increased metabolic activity usually provides energy and nutrients for biomass synthesis and is indispensable for the progression of the cell cycle. Here, we found an unexpected role for α-ketoglutarate (αKG) generation in regulating cell cycle gene transcription. A reduction in cellular αKG levels triggered by malic enzyme 2 (ME2) or isocitrate dehydrogenase 1 (IDH1) depletion leads to a pronounced arrest in G1 phase, while αKG supplementation promotes cell cycle progression. Mechanistically, αKG directly binds to RNA polymerase II (RNAPII), increasing the level of RNAPII binding to the cyclin D1 gene promoter, consequently enhancing cyclin D1 transcription. Notably, αKG addition is sufficient to restore cyclin D1 expression in ME2- or IDH1- depleted cells, facilitating cell cycle progression and proliferation in these cells. Therefore, our findings reveal a previously unappreciated function of αKG in gene transcriptional regulation and cell cycle control.

2023-06-25 | GSE221723 | GEO

CTCF translates IL-2- and αKG-sensitive metabolic changes in T cells into context-dependent differentiation gene programs [ATAC-Seq]

Project description:We found that aspects of the IL-2-sensitive effector gene program in CD4+ Th1 and CD8+ Tc1 cells are regulated by glutamine and alpha-ketoglutarate (αKG)-induced events, in part through changes in DNA and histone methylation states. We further identified a novel mechanism by which IL-2- and αKG-sensitive metabolic changes regulate the association of CTCF with select genomic sites. αKG-sensitive CTCF sites were often associated with loci containing IL-2- and αKG-sensitive genome organization patterns and gene expression in T cells. Surprisingly, IL-2- and αKG-sensitive CTCF sites in T cells were also associated with genes from developmental pathways that had αKG-sensitive expression in ES cells. The data collectively support a novel mechanism wherein CTCF serves to translate αKG-sensitive metabolic changes into context-dependent differentiation gene programs.

2017-08-15 | GSE89038 | GEO

CTCF translates IL-2- and αKG-sensitive metabolic changes in T cells into context-dependent differentiation gene programs [ChIP-Seq]

2017-08-15 | GSE88857 | GEO

CTCF translates IL-2- and αKG-sensitive metabolic changes in T cells into context-dependent differentiation gene programs [RNA-Seq]

2017-08-15 | GSE88829 | GEO

CTCF translates IL-2- and αKG-sensitive metabolic changes in T cells into context-dependent differentiation gene programs [HiC-Seq]

2017-08-15 | GSE89676 | GEO

αKG treatment prevent maturation and stimulate proliferation of neonatal cardiomyocytes

Project description:αKG treatment prevent maturation and stimulate proliferation of neonatal cardiomyocytes

| PRJNA897885 | ENA

Redirected nuclear glutamate dehydrogenase supplies Tet3 with α-ketoglutarate in neurons

Project description:Tet3 is the main α-ketoglutarate (αKG)-dependent dioxygenase in neurons that converts 5-methyl-dC into 5-hydroxymethyl-dC and further on to 5-formyl- and 5-carboxy-dC. Neurons possess high levels of 5-hydroxymethyl-dC that further increase during neural activity to establish transcriptional plasticity required for learning and memory functions. How αKG, which is mainly generated in mitochondria as an intermediate of the tricarboxylic acid cycle, is made available in the nucleus has remained an unresolved question in the connection between metabolism and epigenetics. We show that in neurons the mitochondrial enzyme glutamate dehydrogenase, which converts glutamate into αKG in an NAD+-dependent manner, is redirected to the nucleus by the αKG-consumer protein Tet3, suggesting on-site production of αKG. Further, glutamate dehydrogenase has a stimulatory effect on Tet3 demethylation activity in neurons, and neuronal activation increases the levels of αKG. Overall, the glutamate dehydrogenase-Tet3 interaction might have a role in epigenetic changes during neural plasticity.

2021-06-24 | MTBLS2852 | MetaboLights

Alpha-ketoglutarate -mediated carnitine synthesis promotes homologous recombination via histone acetylation

Project description:Homologous recombination (HR) deficiency enhances sensitivity to DNA damaging agents commonly used to treat cancer. In HR-proficient cancers, metabolic mechanisms driving response or resistance to DNA damaging agents remain unclear. Here we identified that depletion of alpha-ketoglutarate (αKG) sensitizes HR-proficient cells to DNA damaging agents by metabolic regulation of histone acetylation. αKG is required for the activity of αKG-dependent dioxygenases (αKGDDs), and prior work has shown that changes in αKGDD affect demethylases. Using a targeted CRISPR knockout library consisting of 64 αKGDDs, we discovered that Trimethyllysine Hydroxylase Epsilon (TMLHE), the first and rate-limiting enzyme in de novo carnitine synthesis, is necessary for proliferation of HR-proficient cells in the presence of DNA damaging agents. Unexpectedly, αKG-mediated TMLHE-dependent carnitine synthesis was required for histone acetylation, while histone methylation was affected but dispensable. The increase in histone acetylation via αKG-dependent carnitine synthesis promoted HR-mediated DNA repair through site- and substrate-specific histone acetylation. These data demonstrate for the first time that HR-proficiency is mediated through αKG directly influencing histone acetylation via carnitine synthesis and provide a metabolic avenue to induce HR-deficiency and sensitivity to DNA damaging agents.

2025-02-26 | GSE289735 | 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