Related Experiment Video
Updated: Mar 10, 2026

Evaluation of the Spatial Distribution of γH2AX following Ionizing Radiation
Published on: August 7, 2010
Histone H3 Lysine 9 Acetylation Obstructs ATM Activation and Promotes Ionizing Radiation Sensitivity in Normal Stem
Barbara Meyer1, Maria Rita Fabbrizi1, Suyash Raj1
1Cancer Biology Division, Department of Radiation Oncology, Washington University School of Medicine, 4511 Forest Park, Saint Louis, MO 63108, USA.
Abstract:
Dynamic spatiotemporal modification of chromatin around DNA damage is vital for efficient DNA repair. Normal stem cells exhibit an attenuated DNA damage response (DDR), inefficient DNA repair, and high radiosensitivity. The impact of unique chromatin characteristics of stem cells in DDR regulation is not yet recognized. We demonstrate that murine embryonic stem cells (ES) display constitutively elevated acetylation of histone H3 lysine 9 (H3K9ac) and low H3K9 tri-methylation (H3K9me3). DNA damage-induced local deacetylation of H3K9 was abrogated in ES along with the subsequent H3K9me3. Depletion of H3K9ac in ES by suppression of monocytic leukemia zinc finger protein (MOZ) acetyltransferase improved ATM activation, DNA repair, diminished irradiation-induced apoptosis, and enhanced clonogenic survival. Simultaneous suppression of the H3K9 methyltransferase Suv39h1 abrogated the radioprotective effect of MOZ inhibition, suggesting that high H3K9ac promoted by MOZ in ES cells obstructs local upregulation of H3K9me3 and contributes to muted DDR and increased radiosensitivity.
Related Concept Videos
DNA Damage can Stall the Cell Cycle
DNA Damage Can Stall the Cell Cycle
Histone Modification
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Abnormal Proliferation
Spreading of Chromatin Modifications
Writers
The writer...
PI3K/mTOR/AKT Signaling Pathway

