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Histone methylation in Gpt2 KO and Gpt2 WT mouse brain tissues

GSE325503 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 21 samples Submitted 2026/08/01 Platform GPL30172
Summary
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.
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Direct links to NCBI, no account and no request form: the whole study as GSE325503_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 21 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1440355 and SRA study SRP685388. Searching any of these in the dataset finder brings you back here.

Study design
21 conditions, each sampled once — no replicated groups

Read from 21 sample titles: 21 distinct titles with little repetition. Check it against the sample list below before relying on it.

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