Omics · study · 2026
Nuclear class 3 PI3K co-activates fasting-specific chromatin remodeling
Listed in NCBI GEO
Transcriptional remodeling is essential for stress adaptation such as in fasting.
Description
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.
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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.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE290nnn/GSE290681 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290681 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1229528 ncbi.nlm.nih.gov/bioproject/PRJNA1229528 ↗
project · from NCBI GEO
- PubMed 42521791 pubmed.ncbi.nlm.nih.gov/42521791 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
Related
- Possibly the same asNuclear class 3 PI3K co-activates fasting-specific chromatin remodeling
- Possibly the same asNuclear class 3 PI3K co-activates fasting-specific chromatin remodeling
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE290681 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |