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Purification of H3 and H4 Histone Proteins and the Quantification of Acetylated Histone Marks in Cells and Brain Tissue
Published on: November 30, 2018
Nickel compounds are novel inhibitors of histone H4 acetylation
1Department of Environmental Medicine, New York University School of Medicine, New York 10016, USA.
Abstract:
Environmental factors influence carcinogenesis by interfering with a variety of cellular targets. Carcinogenic nickel compounds, although generally inactive in most gene mutation assays, induce chromosomal damage in heterochromatic regions and cause silencing of reporter genes when they are located near telomere or heterochromatin in either yeast or mammalian cells. We studied the effects of nickel on the lysine acetylation status of the NH2-terminal region of histone H4. At nontoxic levels, nickel decreased the levels of histone H4 acetylation in vivo in both yeast and mammalian cells, affecting only lysine 12 in mammalian cells and all of the four lysine residues in yeast. In yeast, lysine 12 and 16 were more greatly affected than lysine 5 and 8. Interestingly, a histidine Ni2+ anchoring site is found at position 18 from the NH2-terminal tail of H4. Nickel was also found to inhibit the acetylation of H4 in vitro using purified recombinant histone acetyltransferase. To our knowledge, this is the first agent shown to decrease histone H4 acetylation at nontoxic levels.
Insights
Nickel compounds, at non-toxic levels, reduce histone H4 acetylation in yeast and mammalian cells. This finding is the first to show an agent decreasing histone H4 acetylation without toxicity.
Area of Science:
- Environmental carcinogenesis
- Molecular biology
- Epigenetics
Background:
- Environmental factors, such as nickel compounds, can influence carcinogenesis.
- Nickel compounds are known to cause chromosomal damage and gene silencing.
- The epigenetic modifications of histone proteins are crucial in regulating gene expression.
Purpose of the Study:
- To investigate the effect of nickel on histone H4 acetylation.
- To determine if nickel affects histone acetylation at non-toxic levels.
- To explore the mechanism of nickel-induced gene silencing.
Main Methods:
- Studied the effect of nickel on histone H4 acetylation in vivo in yeast and mammalian cells.
- Analyzed the acetylation status of specific lysine residues in histone H4.
- Investigated the effect of nickel on histone acetylation in vitro using purified histone acetyltransferase.
Main Results:
- Nickel decreased histone H4 acetylation at non-toxic levels in both yeast and mammalian cells.
- In mammalian cells, nickel affected lysine 12 acetylation; in yeast, it affected all four lysine residues, with lysines 12 and 16 being most impacted.
- Nickel inhibited histone H4 acetylation in vitro, suggesting a direct effect on histone acetyltransferase.
Conclusions:
- Nickel is the first identified agent to decrease histone H4 acetylation at non-toxic levels.
- Nickel-induced changes in histone acetylation may contribute to its carcinogenic effects.
- Further research is warranted to elucidate the precise mechanisms of nickel's epigenetic modifications and their role in carcinogenesis.
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