Iron Oxide Nanoparticles with and without Cobalt Functionalization Provoke Changes in the Transcription Profile via Epigenetic Modulation of Enhancer Activity

[Image: see text] Despite the progress in the field of nanotoxicology, much about the cellular mechanisms that mediate the adverse effects of nanoparticles (NPs) and, in particular, the possible role of epigenetics in nanotoxicity, remains to be clarified. Therefore, we studied the changes occurring in the genome-wide distribution of H3K27ac, H3K4me1, H3K9me2, and H3K27me3 histone modifications and compared them with the transcriptome after exposing NIH3T3 cells to iron-based magnetic NPs (i.e., Fe(2)O(3) and Fe(2)O(3)@Co NPs). We found that the transcription response is mainly due to changes in the genomic distribution of H3K27ac that can modulate the activity of enhancers. We propose that alteration of the epigenetic landscape is a key mechanism in defining the gene expression program changes resulting in nanotoxicity. With this approach, it is possible to construct a data set of genomic regions that could be useful for defining toxicity in a manner that is more comprehensive than what is possible with the present toxicology assays.