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Updated: Apr 19, 2026
Purification of H3 and H4 Histone Proteins and the Quantification of Acetylated Histone Marks in Cells and Brain Tissue
Published on: November 30, 2018
In vitro ischemia decreases histone H4K16 acetylation in neural cells
Ruslan I Dmitriev1, Dmitri B Papkovsky1
1School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland.
Abstract:
Inhibitors of histone deacetylases are frequently used against ischemia-induced injury, but the specific mechanisms of their action are poorly understood. Here, we report that following a 5-7-h oxygen-glucose deprivation (OGD) acetylation of histone H4 at residue K16 (H4K16Ac) decreases by 40-80% in both PC12 cells and primary neurons. This effect can be reverted by treatment with trichostatin A, or by supplementation with acetyl-CoA. A decrease in H4K16Ac levels can affect the expression of mitochondrial uncoupling protein 2 (UCP2), huntingtin-interacting protein 1 (HIP1) and Notch-pathway genes in a cell-specific manner. Thus, H4K16 acetylation is important for responses to ischemia and cell energy stress, and depends on both cytosolic and mitochondrial acetyl-CoA.
Insights
Histone H4K16 acetylation decreases during oxygen-glucose deprivation (OGD) and ischemia. Restoring this acetylation impacts gene expression, highlighting its role in cellular energy stress responses.
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- Histone deacetylase inhibitors are used for ischemia-induced injury.
- Mechanisms underlying their action remain unclear.
- Histone acetylation plays a critical role in gene regulation.
Purpose of the Study:
- To investigate the role of histone H4K16 acetylation in response to oxygen-glucose deprivation (OGD).
- To explore the impact of altered H4K16 acetylation on gene expression.
- To understand the dependence of H4K16 acetylation on acetyl-CoA.
Main Methods:
- Oxygen-glucose deprivation (OGD) in PC12 cells and primary neurons.
- Treatment with trichostatin A.
- Supplementation with acetyl-CoA.
- Analysis of H4K16 acetylation levels and gene expression.
Main Results:
- OGD caused a 40-80% decrease in H4K16 acetylation.
- Trichostatin A and acetyl-CoA supplementation reverted this decrease.
- Altered H4K16Ac levels affected expression of UCP2, HIP1, and Notch-pathway genes.
- H4K16 acetylation levels were dependent on both cytosolic and mitochondrial acetyl-CoA.
Conclusions:
- H4K16 acetylation is crucial for cellular responses to ischemia and energy stress.
- The regulation of H4K16 acetylation is linked to acetyl-CoA availability.
- Understanding these mechanisms can inform therapeutic strategies for ischemia.
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