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Henneman, N.F.* ; Kawamura, G.* ; Luo, Y.* ; Dias, C.O.* ; Su, J.* ; Segaloni, A.* ; Nemazanyy, I.* ; Cam, S.L.* ; Rodrigues, C.* ; Kuperwasser, N.* ; Cagnard, N.* ; Hnia, K.* ; Margueron, R.* ; Lutter, D. ; Ozawa, T.* ; Panasyuk, G.*

Nuclear class 3 PI3K co-activates fasting-specific chromatin remodelling.

Nat. Cell Biol., 42 (2026)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Transcriptional remodelling during fasting ensures metabolic adaptation and provides health benefits across species. Although several regulators of fasting-induced transcription and chromatin are known, how nutrient levels directly influence RNA polymerase II (RNAPII) and epigenetic writers remains unclear. Here we show that lipid kinase class 3 phosphatidylinositol 3-kinase (PI3K-3), a master regulator of autophagy, also functions on chromatin as a co-activator of epigenetic writers to promote RNAPII transcription. PI3K-3 overlaps with transcriptionally engaged RNAPII phosphorylated at Ser5 and with Setd1a/COMPASS, the complex that deposits the activating H3K4me3 mark. Nuclear PI3K-3 interacts with RNAPII and Setd1a/COMPASS and promotes their chromatin binding. PI3K-3 loss reduces RNAPII-S5p and H3K4me3 at selected genes, whereas PI3K-3 overexpression co-activates p300/CBP and chromatin-targeted PI3K-3 increases H3K4me3. During starvation, PI3K-3 induces autophagy genes and drives fasted liver towards ketogenesis and lipid degradation. These findings link nutrient stress to chromatin-mediated transcriptional activation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Chromatin ; H3k4me3 ; Epigenetics ; Rna Polymerase Ii ; Transcriptional Regulation ; Transcription (linguistics) ; Regulator ; Phosphatidylinositol ; Pi3k/akt/mtor Pathway; Rna-polymerase; Phosphatidylinositol 3-kinase; Transcriptional Elongation; Epigenetic Regulation; Methylation; Complexes; Autophagy; Inhibition; Expression
ISSN (print) / ISBN 1465-7392
e-ISSN 1476-4679
Zeitschrift Nature Cell Biology
Quellenangaben Band: , Heft: , Seiten: 42 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort Heidelberger Platz 3, Berlin, 14197, Germany
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Förderungen Deutsche Forschungsgemeinschaft (German Research Foundation)
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)