Mercury chloride alters heterochromatin domain organization and nucleolar activity in mouse liver

Abstract

Mercury is a highly toxic element that induces severe alterations and a broad range of adverse effects on health. Its exposure is a global concern because it is widespread in the environment due to its multiple industrial, domestic, agricultural and medical usages. Among its various chemical forms, both humans and animals are mainly exposed to mercury chloride (HgCl2), methylmercury and elemental mercury. HgCl2 is metabolized primarily in the liver. We analysed the effects on the nuclear architecture of an increasing dosage of HgCl2 in mouse hepatocytes cell culture and in mouse liver, focusing specifically on the organization, on some epigenetic features of the heterochromatin domains and on the nucleolar morphology and activity. Through the combination of molecular and imaging approaches both at optical and electron microscopy, we show that mercury chloride induces modifications of the heterochromatin domains and a decrease of some histones post-translational modifications associated to heterochromatin. This is accompanied by an increase in nucleolar activity which is reflected by bigger nucleoli. We hypothesized that heterochromatin decondensation and nucleolar activation following mercury chloride exposure could be functional to express proteins necessary to counteract the harmful stimulus and reach a new equilibrium.

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

“…These data suggest that heterochromatin is not involved in defining the transcriptional changes caused by treatment with the two NPs. However, due to the dynamic nature of histone modifications, and the crosstalk between different epigenetic marks, 39 we cannot exclude the possibility that H3K9me2 and H3K27me3 could act either before or after the time point that we analyzed (48 h), or the involvement of other repressive epigenetic mechanisms (e.g., DNA methylation, H3K9me3, and H4K20me3) in mediating the effect of the two NPs on heterochromatin.…”

“…Impairment of this type of chromatin organization can lead to alterations of gene expression programs causing several diseases . Recent studies have also suggested a role of heterochromatin in mediating the effects of various stress stimuli. , Although these findings render heterochromatin an enticing target for understanding the molecular mechanisms of nanotoxicity, we did not detect the involvement of H3K9me2 and H327me3, two key histone modifications regulating heterochromatin organization, in defining the changes in transcription caused by NPs and their corresponding ions (i.e., iron and cobalt). These data suggest that heterochromatin is not involved in defining the transcriptional changes caused by treatment with the two NPs.…”

In focus in HCB

“…In their present study, Zannino et al (2022) analyzed the effect of a 1 h treatment with 1, 5, and 10 μM HgCl 2 on the nucleus of the AML 12 mouse hepatocyte cell line and liver explants from 3-month-old B6C3F1 mice. Conventional histochemical reactions for staining of ultrathin sections such as the EDTA regressive technique and AgNOR and osmium ammine staining were applied, as well as Hoechst staining, immunogold electron microscopy, western blotting, and RT-qPCR.…”