Epigenetics is the study of heritable changes in gene expression that occur without alterations in the DNA sequence. Several studies have shown that environmental chemicals can alter epigenetic modifications, including histone modifications and DNA methylation. Environmental chemicals may show toxic effects via epigenetic mechanism-regulated changes in gene expression. Previously, we reported that zinc treatment rapidly decreased Lys(4)-trimethylated and Lys(9)-acetylated histone H3 in the metallothionein (MT) promoter, and also decreased total histone H3. The chromatin structure in the MT promoter may be locally disrupted by zinc-induced nucleosome removal. We also showed that chromium (VI) inhibited MT gene transcription by modifying the transcription potential of the co-activator p300. MT is a small cysteine-rich protein that is active in zinc homeostasis, cadmium detoxification, and protection against reactive oxygen species. Epigenetic changes might influence the cytoprotective function of the MT gene. In this review, I briefly summarize the results of previous studies and discuss the mechanisms and toxicological significance of metal-mediated epigenetic modifications.