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Updated: May 25, 2026
09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Functional interplay between p53 acetylation and H1.2 phosphorylation in p53-regulated transcription
1Department of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine, Los Angeles, CA 90089, USA.
Oncogene
|January 18, 2012
Summary
Histone H1.2 normally suppresses gene activity, but its repression of p53 is reversed by p53 acetylation and H1.2 phosphorylation, activating DNA damage responses.
Area of Science:
- Molecular Biology
- Cellular Biology
- Epigenetics
Background:
- Linker histone H1.2 modulates chromatin remodeling to suppress p53-dependent transcription.
- Mechanisms underlying H1.2's antagonistic effects in DNA damage response remain unclear.
Purpose of the Study:
- Investigate the regulatory mechanisms controlling H1.2's repressive function on p53 during DNA damage.
- Elucidate how post-translational modifications of p53 and H1.2 impact their interaction and p53 activity.
Main Methods:
- Assessed the impact of p53 acetylation and H1.2 phosphorylation on the p53-H1.2 interaction.
- Utilized point mutations to mimic specific modification states of p53 and H1.2.
- Measured p53-dependent transcriptional activity and apoptosis induction.
Main Results:
- p53 acetylation by p300 disrupts p53-H1.2 binding, leading to p53 transcriptional activation.
- DNA-PK-mediated phosphorylation of H1.2 at T146 also impairs H1.2 binding to p53, enhancing transcriptional activity.
- Mutations mimicking these modifications significantly increased p53-induced apoptosis.
Conclusions:
- A p53 acetylation-H1.2 phosphorylation cascade regulates H1.2's suppressive role in DNA damage response.
- This cascade acts as a critical switch for activating p53-dependent DNA damage pathways.
- Findings reveal a novel mechanism for fine-tuning the cellular response to DNA damage.
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