Fig. 1

Epigenetic regulations in normal cells and after exposure to nanomaterials and nanoparticles. In normal cells, epigenetic mechanisms are well controlled and maintained by coordinated functioning of chromatin-modifying proteins, e.g., DNA methyltransferases, DNA demethylases, histone protein “writers” and “erasers”. In general, the epigenetic landscape of the normal genome consists of short unmethylated cytosine (white circles) enriched domains containing histone transcription activating modifications, including histone H3K4me3, H3K36me3, H3K9ac, and H3K27ac (green hexagons), predominantly located at the 5′-gene regions. These regions are embedded in a matrix of long methylated cytosine (red circles) domains containing both histone transcription activating (green hexagons) and transcription inactivating marks (yellow hexagons). The accurate balance between these epigenetic modifications is critical for the proper maintenance of chromatin structure and gene expression. a Exposure to NMs and NPs reshapes the epigenetic genome landscape by increasing cytosine DNA methylation (red circles) and histone transcription inactivating modifications (yellow hexagons), including increased histone H3K9 and H3K27 methylation, decreased histone K3K4 and H3K36 methylation, and loss of histone acetylation at the 5′-gene regions. Additionally, exposure to NMs and NPs causes damage to DNA (red triangle) across the genome and demethylation of cytosines (white circles) of previously methylated DNA domains. All these exposure-related events result in compromised chromatin structure and aberrant gene expression (b)