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DOI
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as soon as is submitted to ZB.
Nuclear class 3 PI3K co-activates fasting-specific chromatin remodelling.
Nat. Cell Biol., 42 (2026)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
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
Journal
Nature Cell Biology
Quellenangaben
Pages: 42
Publisher
Nature Publishing Group
Publishing Place
Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)
Grants
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)
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)