It is known that histone modifications may interfere with epigenetic changes in neutrophils. Histone H3 citrullination leads to chromatin decondensation and promotes DNA cleavage which results in altered gene expression profile.
We hypothesize that hypoxia enhances the activity of peptidyl arginine deiminase and the production of citrullinated proteins, including histone H3 proteins in neutrophils. Altered gene expression is in-turn, manifested by functional variability in neutrophils. Emerging evidence suggests this as an important pathological mechanism in chronic inflammatory diseases such as arthritis. Since histone protein citrullination is not the only epigenetic mechanism contributing to the functional plasticity in neutrophils, we also evaluate the effects of hypoxia on histone methylation and acetylation status in neutrophils.