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Nuclear class 3 PI3K co-activates fasting-specific chromatin remodeling

GSE290682 Homo sapiens; Mus musculus Genome binding/occupancy profiling by high throughput sequencing 63 samples Submitted 2026/06/02 Platform GPL28457Platform GPL28038
Summary
Transcriptional remodeling is essential for stress adaptation such as in fasting. While the core transcriptional machinery and its regulators are known, how information regarding energy availability is relayed to transcriptional complexes remains unclear. Surprisingly, we find that class 3 Phosphatidyl inositol-3 kinase (PI3K-3) lipid kinase, a master regulator of cytosolic autophagy, co-activates epigenetic writers for fasting-induced transcription. To this end, chromatin distribution of PI3K-3 significantly overlapped with transcriptionally engaged RNA Pol II phosphorylated on Ser5 (RNAPII-S5p) and transcriptionally permissive H3K4me3. Mechanistically, nuclear PI3K-3 interacted with both RNAPII and the Set1a/COMPASS methyltransferase of H4K4me3. Moreover, decreased binding between RNAPII and Set1a/COMPASS was found in PI3K-3 depleted cells. Accordingly, PI3K-3 deletion led to lower H3K4me3 and RNAPII-S5p enrichment at selective loci. Conversely, PI3K-3 overexpression co-activated acetyltransferase p300/CBP in luciferase assays while its chromatin targeting promoted H3K4me3 deposition. In starved cells, PI3K-3 induced transcription of autophagy-related genes, and in fasted liver, it was critical for transcriptional remodeling of metabolism, such as activation of lipid degradation. Thus, PI3K-3 couples nutrient availability to chromatin remodeling for transcriptional activation, enabling metabolic adaptation in fasting.
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Direct links to NCBI, no account and no request form: the whole study as GSE290682_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 63 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1229530 and SRA study SRP566832. Searching any of these in the dataset finder brings you back here.

Study design
13 conditions, mostly in duplicate
RNA Pol II S5P, liver, Fed Vps15LKO, ×3 RNA Pol II S5P, liver, Fast Vps15LKO, ×3 Vps15, liver, Fast wt, ×3 Vps15, liver, Fed wt, ×2 H3K4me3, liver, Fed wt, ×2 H3K4me3, liver, Fast wt, ×2 H3K4me3, liver, Fed Vps15LKO, ×2 H3K4me3, liver, Fast Vps15LKO, ×2 +16 more

Supports a case/control comparison: 9 samples read as cases, 17 as controls.

13 replicated groups read from the first 40 of 63 sample titles; they account for 29 of them. Check it against the sample list below before relying on it.

Samples in this study

+ 23 more — browse all 63 samples with per-sample file links →

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