概括
早期接触有毒化学物质会导致表观基因组和转录基因组的长期变化. 转录II的基因组和表观基因组调节器 (TaRGET II) 联盟提供了一个公共资源来研究这些影响.
科学领域:
- 环境表观遗传学
- 毒基因组学
- 分子毒理学
背景情况:
- 环境中毒物会破坏基因表达和表观遗传调节.
- 这些干扰可以导致整个生命的疾病.
- 了解早期暴露的长期分子后果至关重要.
研究的目的:
- 创建一个全面的资源,详细说明各种毒素的表观基因和转录基因效应.
- 研究这些分子变化的持续性和特异性.
- 为研究环境暴露与疾病之间的联系提供可访问的数据.
主要方法:
- 在暴露于特定毒素 (,,BPA,DEHP,TBT,TCDD,PM2.5) 的小鼠中进行了长度研究.
- 从不同生命阶段的多种组织生成2570个表观基因组和1043个转录基因组.
- 对DNA甲基化,染色质可访问性和基因表达模式的分析.
主要成果:
- 在表观基因组和转录基因组中发现了持久的,毒素特异性的和性别依赖的变化.
- 观察到广泛的基因表达干扰 (14,908个基因),染色质可访问性改变 (87,409个元素) 和DNA甲基化变化 (113,186个区域).
- 在毒性暴露后记录了染色体状态的切换.
结论:
- 在生命早期的环境暴露可以以持久的方式重新编程表观基因组和转录基因组.
- 塔格特II资源提供了这些分子变化的高分辨率地图.
- 这些公开可用的数据有助于研究环境引起的疾病的病原性.
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