Related Experiment Video
Updated: Jun 26, 2026
Site Specific Lysine Acetylation of Histones for Nucleosome Reconstitution using Genetic Code Expansion in Escherichia coli
Published on: December 26, 2020
Acetylation curtails nucleosome binding, not stable nucleosome remodeling, by FoxO1
1Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Abstract:
Transcriptional activity of FoxO factors is controlled through the actions of multiple growth factors signaling through protein kinase B, whereby phosphorylation of FoxO factors inhibits FoxO-mediated transactivation by promoting nuclear export. Phosphorylation of FoxO factors is enhanced by p300-mediated acetylation, which decreases their affinity for DNA. The negative effect of acetylation on FoxO DNA binding, together with nuclear FoxO mobility, is eliminated by over-expression of the de-acetylase Sirt1, suggesting that acetylation mobilizes FoxO factors in chromatin for inducible gene expression. Here, we show that acetylation significantly curtails the affinity of FoxO1 for its binding sites in nucleosomal DNA but has no effect on either stable nucleosome binding or remodeling by this factor. We suggest that, while acetylation provides a first, essential step toward mobilizing FoxO factors for inducible gene repression, additional mechanisms exist for overcoming their inherent capacity to stably bind and remodel nuclear chromatin.
Insights
Acetylation of Forkhead box O (FoxO) factors curtails their DNA binding affinity, impacting gene regulation. However, Sirtuin 1 (Sirt1) can overcome this effect, suggesting complex mechanisms control FoxO-mediated gene expression.
Area of Science:
- Molecular Biology
- Gene Regulation
- Epigenetics
Background:
- Forkhead box O (FoxO) transcription factors regulate gene expression.
- Their activity is modulated by growth factor signaling, phosphorylation, and post-translational modifications like acetylation.
- Acetylation by p300 decreases FoxO DNA binding affinity, while Sirt1 can reverse this effect.
Purpose of the Study:
- To investigate the precise impact of acetylation on FoxO1 binding to nucleosomal DNA.
- To determine if acetylation affects FoxO1's ability to bind and remodel nucleosomes.
- To elucidate the role of acetylation in mobilizing FoxO factors for gene regulation.
Main Methods:
- In vitro assays to assess FoxO1 binding affinity to DNA and nucleosomes.
- Chromatin immunoprecipitation (ChIP) assays.
- Analysis of FoxO1-mediated gene expression.
Main Results:
- Acetylation significantly reduces FoxO1's affinity for its binding sites within nucleosomal DNA.
- Acetylation does not affect FoxO1's stable binding to nucleosomes.
- Acetylation does not alter FoxO1's nucleosome remodeling activity.
- Overexpression of Sirt1 mitigates the negative impact of acetylation on FoxO1 DNA binding.
Conclusions:
- Acetylation is an initial step in mobilizing FoxO factors for inducible gene repression.
- Additional mechanisms are required to overcome FoxO1's inherent ability to bind and remodel chromatin.
- Understanding these acetylation-dependent mechanisms is crucial for controlling gene expression and cellular responses.
More Related Videos
10:28Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
10:09Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
Related Concept Videos
02:54Nucleosome Remodeling
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
02:32Histone Modification
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:32Histone Modification
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:25Spreading of Chromatin Modifications
Writers
The writer is an enzyme that can...
01:32Chromatin Modification in iPS Cells
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
01:12The Nucleosome Core Particle
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...