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Chromatin Immunoprecipitation (ChIP) to Assay Dynamic Histone Modification in Activated Gene Expression in Human Cells
Published on: July 29, 2010
Nuclear class 3 PI3K co-activates fasting-specific chromatin remodelling
Nathaniel F Henneman1,2, Genki Kawamura3, Ying Luo1,2
1Institut Necker-Enfants Malades, INSERM U1151/CNRS UMR 8253, Paris, France.
Nature Cell Biology
|July 28, 2026
Summary
Lipid kinase PI3K-3 acts on chromatin to boost RNA polymerase II transcription and epigenetic marks during fasting. This discovery links nutrient stress to gene regulation, impacting metabolic adaptation and health.
Area of Science:
- Molecular Biology
- Epigenetics
- Metabolism
Background:
- Fasting induces metabolic adaptation through transcriptional changes.
- Regulators of fasting-induced transcription and chromatin are known, but nutrient sensing mechanisms remain unclear.
- The direct influence of nutrient levels on RNA polymerase II (RNAPII) and epigenetic writers is not well understood.
Purpose of the Study:
- To investigate the role of lipid kinase class 3 phosphatidylinositol 3-kinase (PI3K-3) in nutrient-mediated transcriptional regulation during fasting.
- To determine how PI3K-3 influences RNA polymerase II (RNAPII) activity and epigenetic modifications.
- To elucidate the link between nutrient stress, chromatin regulation, and metabolic adaptation.
Main Methods:
- Chromatin immunoprecipitation assays to assess RNAPII and H3K4me3.
- Co-immunoprecipitation to study protein interactions.
- Gene expression analysis to evaluate the impact of PI3K-3 on target genes.
- Overexpression and knockdown studies of PI3K-3.
Main Results:
- PI3K-3 localizes to chromatin and co-activates epigenetic writers, promoting RNAPII transcription.
- PI3K-3 interacts with RNAPII and Setd1a/COMPASS, enhancing their chromatin binding.
- Loss of PI3K-3 reduces RNAPII phosphorylation and H3K4me3 levels, while its overexpression increases H3K4me3.
- PI3K-3 induces autophagy genes during starvation, promoting ketogenesis and lipid degradation in the liver.
Conclusions:
- PI3K-3 is a key regulator linking nutrient stress to chromatin-mediated transcriptional activation.
- PI3K-3 functions as a co-activator of epigenetic writers, influencing RNAPII transcription and metabolic adaptation.
- These findings reveal a novel mechanism by which nutrient levels directly impact gene expression and cellular metabolism during fasting.
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