Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Harvard School of Public Health, Boston, MA, USA.
Part Fibre Toxicol. 2013 Jul 15;10:28. doi: 10.1186/1743-8977-10-28.
Repetitive elements take up >40% of the human genome and can change distribution through transposition, thus generating subfamilies. Repetitive element DNA methylation has associated with several diseases and environmental exposures, including exposure to airborne pollutants. No systematic analysis has yet been conducted to examine the effects of exposures across different repetitive element subfamilies. The purpose of the study is to evaluate sensitivity of DNA methylation in differentially‒evolved LINE, Alu, and HERV subfamilies to different types of airborne pollutants.
We sampled a total of 120 male participants from three studies (20 high-, 20 low-exposure in each study) of steel workers exposed to metal-rich particulate matter (measured as PM10) (Study 1); gas-station attendants exposed to air benzene (Study 2); and truck drivers exposed to traffic-derived elemental carbon (Study 3). We measured methylation by bisulfite-PCR-pyrosequencing in 10 differentially‒evolved repetitive element subfamilies.
High-exposure groups exhibited subfamily-specific methylation differences compared to low-exposure groups: L1PA2 showed lower DNA methylation in steel workers (P=0.04) and gas station attendants (P=0.03); L1Ta showed lower DNA methylation in steel workers (P=0.02); AluYb8 showed higher DNA methylation in truck drivers (P=0.05). Within each study, dose-response analyses showed subfamily-specific correlations of methylation with exposure levels. Interaction models showed that the effects of the exposures on DNA methylation were dependent on the subfamily evolutionary age, with stronger effects on older LINEs from PM10 (p‒interaction=0.003) and benzene (p‒interaction=0.04), and on younger Alus from PM10 (p-interaction=0.02).
The evolutionary age of repetitive element subfamilies determines differential susceptibility of DNA methylation to airborne pollutants.
重复元件占据人类基因组的>40%，通过转座可改变其分布，从而产生亚家族。重复元件的 DNA 甲基化与多种疾病和环境暴露有关，包括暴露于空气污染物。目前尚未进行系统分析以检查不同重复元件亚家族暴露的影响。本研究旨在评估不同进化的 LINE、Alu 和 HERV 亚家族中 DNA 甲基化对不同类型空气污染物的敏感性。
我们从三个研究（每个研究中有 20 名高暴露和 20 名低暴露的男性参与者）中总共抽取了 120 名男性参与者，这些参与者分别是暴露于富含金属的颗粒物（以 PM10 衡量）的钢铁工人（研究 1）；暴露于空气苯的加油站服务员（研究 2）；和暴露于交通衍生元素碳的卡车司机（研究 3）。我们通过 bisulfite-PCR-pyrosequencing 测量了 10 个不同进化的重复元件亚家族的甲基化。
高暴露组与低暴露组相比，表现出亚家族特异性的甲基化差异：L1PA2 在钢铁工人（P=0.04）和加油站服务员（P=0.03）中表现出较低的 DNA 甲基化；L1Ta 在钢铁工人中表现出较低的 DNA 甲基化（P=0.02）；AluYb8 在卡车司机中表现出较高的 DNA 甲基化（P=0.05）。在每个研究中，剂量反应分析显示亚家族特异性的甲基化与暴露水平相关。交互模型表明，暴露对 DNA 甲基化的影响取决于重复元件亚家族的进化年龄，PM10（p-交互=0.003）和苯（p-交互=0.04）中的较老 LINEs 以及 PM10 中的较新 Alus （p-交互=0.02）的影响更大。
重复元件亚家族的进化年龄决定了 DNA 甲基化对空气污染物的敏感性差异。
