Sánchez Oscar F, Lin Li F, Xie Junkai, Freeman Jennifer L, Yuan Chongli
Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA.
School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.
Curr Res Toxicol. 2021 Dec 11;3:100061. doi: 10.1016/j.crtox.2021.12.001. eCollection 2022.
Lead (Pb) is a heavy metal contaminant commonly found in air, soil, and drinking water due to legacy uses. Excretion of ingested Pb can result in extensive kidney damages due to elevated oxidative stress. Epigenetic alterations induced by exposure to Pb have also been implied but remain poorly understood. In this work, we assessed changes in repressive epigenetic marks, namely DNA methylation (CpG) and histone 3 lysine 9 tri-methylation (H3K9me3) after exposure to Pb. Live cell epigenetic probes coupled to bimolecular fluorescence complementation (BiFC) were used to monitor changes in the selected epigenetic marks. Exposure to Pb significantly lowered CpG and H3K9me3 levels in HEK293T cells suggesting global changes in constitutive heterochromatin. A heterodimeric pair of probes that tags chromatin regions enriched in both CpG and H3K9me3 further confirmed our findings. The observed epigenetic changes can be partially attributed to aberrant transcriptional changes induced by Pb, such as overexpression of TET1 after Pb exposure. Lastly, we monitored changes in selected heterochromatin marks after removal of Pb and found that changes in these markers do not immediately recover to their original level suggesting potential long-term damages to chromatin structure.
铅（Pb）是一种重金属污染物，由于过去的使用情况，常见于空气、土壤和饮用水中。摄入的铅排泄会因氧化应激升高而导致广泛的肾脏损伤。接触铅引起的表观遗传改变也已被提及，但仍了解甚少。在这项工作中，我们评估了接触铅后抑制性表观遗传标记的变化，即DNA甲基化（CpG）和组蛋白3赖氨酸9三甲基化（H3K9me3）。结合双分子荧光互补（BiFC）的活细胞表观遗传探针用于监测所选表观遗传标记的变化。接触铅显著降低了HEK293T细胞中的CpG和H3K9me3水平，表明组成型异染色质发生了全局变化。一对标记富含CpG和H3K9me3的染色质区域的异二聚体探针进一步证实了我们的发现。观察到的表观遗传变化部分可归因于铅诱导的异常转录变化，如铅暴露后TET1的过表达。最后，我们监测了去除铅后所选异染色质标记的变化，发现这些标记的变化不会立即恢复到原始水平，表明对染色质结构可能存在长期损害。
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