A Novel Post-Translational Modification of Core Histone Proteins: Glutathionylation
Authors:Carl Decker, Oscar Tello
- Jerome Garcia, Associate Professor of Biology, University of La Verne
- Kathleen Weaver, Associate Professor of Biology, University of La Verne
The modification of core histone proteins plays an essential regulatory role in gene transcription, as their structural conformation directly affects the expression of the DNA material coiled around them. Therefore, a better understanding of histone modifiers is critical in gaining further insight into several maladies associated with dysfunctional gene expression, including cancer and neurodegeneration. Aligned with this premise, the objective of this study was to determine if core histone proteins could be modified by glutathione disulfide (GSSG), a tripeptide with known protein interaction capabilities. Core histones were extracted and isolated from a culture of SHSY5Y human neuron cancer cells, and treated with 0.01mM, 0.025mM, 0.05mM, 0.1 mM, 1.0 mM, and 5.0 mM concentrations of GSSG. Histone isolates were then processed through a western blot analysis and visualized via chemiluminescent detection. Subsequently, all core histones (H2A, H2B, H3, and H4) were shown to be glutathionylated in a positive, dose- dependent fashion. To both expand these data and address the limitations of our chemical model, we are now investigating the relationship of nitric oxide (NO) and hydrogen peroxide (H2O2) oxidative stress with SHSY5Y histone glutathionylation under an in- vitro paradigm.