Table 3.
Summary of epigenetic changes induced by neurotoxic metals
| Metal | Epigenetic changes | Consequences of epigenetic changes | References |
|---|---|---|---|
| Manganese (Mn) | Transient hypermethylation of parvalbumin | Disruption of neurogenesis and subsequent neuronal differentiation | (Wang et al., 2013) |
| Hypermethylation of Midi, Atpla3 and Nr2f1 | Disruption of neurogenesis and subsequent neuronal differentiation | (Wang et al., 2013) | |
| Sequestration of DNMT1 via a-synuclein overexpression | (Li et al. 2010; Tarale et al.,2016) | ||
| Hypo-acetylation of histone H3 and H4 via upregulation of HDAC activity and downregulation of HAT activity | Death of dopaminergic neurons | (Guo et al. 2018) | |
| Suppressed expression of miR-133b | Increased proliferation of malignant cells | (Cai et al., 2011) | |
| Downregulation of miR-7 and miR-153 | Overexpression of SNCA gene | (Tarale et al., 2018) | |
| Arsenic (As) | DNA hypomethylation leading to upregulation of ER-α | Formation of proliferative leison and hepatocellular carcinogenesis. | (see review Hussain et al. 2018) |
| Restriction of DNMT activity leading to DNA hypomethylation | Increased activation of K-ras gene in malignant RWPE-1 cells | (Reichard and Puga 2010) | |
| Hypo-acetylation of histone 3K9 | Memory deficits in mice | (Cronican et al. 2013) | |
| Downregulation of miR-199a-5p | Tumor angiogenesis in humsn bronchial epithelium | (He et al. 2014) | |
| Lead(Pb) | Decreased expression of DNMTs and MeCP2 enzymes | Increased risk of AD | (Eid et al. 2016; Sanchez-Martin et al. 2015) |
| Repressed H3K9Ac and H3K4Me2 expression and upregulation of H3K27Me3 | Increased risk of AD | (Eid et al. 2016; Sanchez-Martin et al. 2015) | |
| Inhibition of DNA methylation via alteration of IGF-1 and methionine-stimulated synthase | Impaired cognitive function | (Waly et al. 2004) | |
| Reduced DNA methylation of the PEG3 differentially methylated regions. | Impaired brain development | (Li et al. 2015) | |
| Mercury (Hg) | Decreased expression of BDNF mRNA | Behavioural alterations | (Onishchenko et al. 2008) |
| Overexpression of five major ncRNA (miR-302b, miR-367, miR-372, miR-196b, and miR-141) | Impaired learning and memory, synaptic vesicle transport, and neuronal development. | (Pallocca et al. 2013) | |
| Global DNA hypomethylation of the NSCs | Reduced neural stem cell proliferation | (Bose et al. 2012) | |
| Decreased global DNA methylation and DNMTs activity | Transgenerational inheritance of dysregulated genes | (Basu et al. 2013) | |
| Transgenerational epigenetic alterations of DNA methylation regions. | Trangenerational inheritance of phenotypes (visual deficits and hyperactivity) in zebrafish. | (Carvan et al. 2017) | |
| Nickel (Ni) | increased histone H3K9 dimethylation | transgene silencing in G12 Chinese hamster cells | (Chen et al. 2006) |
| DNA Heterochromatinization | Gpt transgene silencing in Chinese hamster V79-derived G12 and G10 cells | (Ellen et al. 2009) | |
| Dose- and time-dependent (0.2 mM) ubiquitination of H2A and H2B. | Impaired mechanism of DNA repair in cultured 1HAEo- and HPL1D human lung cells | (Karaczyn et al. 2006) | |
| Cadmium (Cd) | DNA hypermethylation and enhanced DNMT activity (chronic exposure, low dose 0–1.5 μmol/L) | Increased cellular proliferation of human embryo lung fibroblast cells. | (Jiang et al. 2008) |
| DNA hypomethylation by means of non-competitive inhibition of DNMT activity, (acute exposure in high dose 2.0μM) | Stimulation of K562 cell proliferation. | (Huang et al. 2008) | |
| Upregulation of H3K4me3, H3K27me3 and H3K9me3 occupancy at the metallothionein 3 (MT3) promoter. | Activation of MT3 gene in human urothelial cell (found in urothelial cancer) (bivalent state) | (Somji et al. 2011) | |
| Inhibition of H3 Phosphorylation via inactivity of the human vaccinia-related kinase VRK1/2. | Defective DNA repair system | (Barcia-Sanjurjo et al. 2013) |