Effects of environmental stressors on histone modifications and their relevance to carcinogenesis: A systematic review

Carcinogenesis is a complex process involving both genetic and epigenetic mechanisms. The cellular molecular epigenetic machinery, including histone modifications, is associated with changes in gene expression induced by exposure to environmental agents. In this paper, we systematically reviewed publications regarding the effects of xenobiotic stressors, mainly heavy metal exposure, on specific histone modifications. We included a total of 18 publications describing the effect of environmental stressors on histone structure modifications. We then constructed an interaction map to visualize the effect of environmental exposure(s) on specific histone modifications. In the studies we considered, a total of 20 modifications were reported, of which H3Me3K4 and H3Me2K9 were the most frequently studied histone modifications. These modifications were affected mostly by heavy metals and ethanol exposure. Based on the interaction map, we explored the molecular mechanisms mediating the histone modifications induced by environmental stressors in the respective selected studies. This resulted in the identification of seven target proteins and two families of proteins mediating the effects of environmental stressors on histone modifications. This review contributes to the understanding of environmental exposure and its possible effects on cancer risk by inducing changes in histone modifications and hence gene expression.