An Investigation of the Effects of Selenium on Histone Acetylation

Open Access
Author:
Tuchinsky, Amanda Kate
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Dr K Sandeep Prabhu, Thesis Supervisor
  • Richard Cyr, Honors Advisor
Keywords:
  • selenium
  • HATs
  • histone acetylation
  • indomethacin
  • HQL-79
Abstract:
Histones are an important component of DNA, affecting both transcription and translation within the cell. DNA in our cells is wound around an octomer of four core histone proteins. Post-translational covalent modifications of these histones at specific residues, including acetylation, methylation, and phosphorylation, can lead to the activation or repression of gene transcription. Histone acetylation, performed by histone acetyltransferases (HATs), is of particular interest because it can lead to the activation of inflammatory genes and pathways in the body. Mutated or malfunctioning HATs can also lead to disease, and may be future targets for cancer therapies. Because of these links between inflammation and disease, it is important to understand histone acetylation and how it is regulated. It has been shown that selenium has anti-inflammatory properties by serving as an antioxidant and by increasing the production of anti-inflammatory prostaglandins in macrophages. Because of the effects of selenium on inflammation, it is believed that selenium may affect HATs and cause a reduction in histone acetylation, decreasing the activation of inflammatory genes. This investigation takes a look at the effects of different concentrations of selenium on histone acetylation on H4K5, H4K8, H4K12, and H4K16 residues in macrophages and hepatocytes. Our results do in fact show that selenium supplementation reduces histone acetylation on H4 residues in both macrophages and hepatocytes.