{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE322778"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Nuclear class 3 PI3K co-activates fasting-specific chromatin remodeling","description":"Transcriptional remodeling in fasting assures metabolic adaptation that provides health benefits across species1-5. While the regulators of transcription and chromatin organization in fasting are known6-10, how lack of nutrients impacts RNA Pol II (RNAPII) and epigenetic writers remains unclear. Surprisingly, we find that class 3 Phosphatidyl inositol-3 kinase (PI3K-3) lipid kinase, a master regulator of autophagy11, is present at chromatin where it co-activates epigenetic writers for transcriptional activation. To this end, the chromatin distribution of PI3K-3 largely overlapped with transcriptionally engaged RNAPII phosphorylated on Ser5 (RNAPII-S5p) and Setd1a/COMPASS, the transcription activating H3K4me3 methyltransferase complex12. Mechanistically, nuclear PI3K-3 interacted with RNAPII and the Set1a/COMPASS transcriptional complexes and facilitated their binding. Accordingly, PI3K-3 deletion resulted in lower H3K4me3 and RNAPII-S5p enrichment at selective loci. Conversely, PI3K-3 overexpression co-activated acetyltransferase p300/CBP while chromatin targeting of PI3K-3 promoted H3K4me3 deposition. In starved cells, PI3K-3 was needed for the transcriptional induction of autophagy-related genes, and in fasted liver, it was critical for metabolic shift, such as ketogenesis and lipid degradation. Thus, PI3K-3 couples nutrient availability to chromatin remodeling enabling adaptive transcriptional activation during nutrient stress.","dates":{"publication":"2026/06/02"},"accession":"GSE322778","cross_references":{"GSM":["GSM9558290","GSM9558292","GSM9558291","GSM9558294","GSM9558283","GSM9558293","GSM9558296","GSM9558285","GSM9558295","GSM9558284","GSM9558298","GSM9558287","GSM9558297","GSM9558286","GSM9558300","GSM9558289","GSM9558299","GSM9558288"],"GPL":["28038"],"GSE":["322778"],"taxon":["Homo sapiens"]}}