亚环蛋白结合CDK4破坏斑马鱼的DNA甲基化 表观遗传学 跨代遗传
Aoxue Wang1, Shiyao Shi1, Yongfang Ma1
1Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou 310058, P. R. China.
Environmental science & technology
|December 8, 2025
概括
农药阿佐环丁 (ACT) 通过向CDK4来破坏DNA甲基化,影响与内分泌相关的基因. 这种分子洞察力解释了ACT.
科学领域:
- 环境毒理学环境毒理学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 环素 (ACT) 是一种具有内分泌干扰作用的有机素农药.
- 以前的研究通过DNA甲基化将ACT与斑马鱼的跨代内分泌干扰联系在一起,但机制尚不清楚.
研究的目的:
- 阐明ACT在斑马鱼ZF4细胞中调节DNA甲基化的分子机制.
- 为了确定ACT表观遗传效应的主要分子标.
主要方法:
- 使用斑马鱼ZF4细胞进行体外研究.
- 进行了5mC量化,全基因组双硫酸盐测序 (WGBS) 和RNA测序 (RNA-seq).
- 进行了西方抹杀,共免疫沉,拉下测试,分子对接和表面等离子体共振 (SPR).
主要成果:
- 暴露在ACT下降了全球DNA甲基化38.03%.
- ACT 失调了与甲基化相关的基因,影响了CDK4/pRb/E2F1/DNMT1信号轴.
- 确认了ACT与循环林依赖激酶4 (CDK4) 的直接结合,确定它是主要的分子标.
结论:
- 通过向CDK4,ACT破坏了DNA甲基化,导致内分泌相关和印记基因的表观遗传变化.
- 这项研究为ACT对水生生物的毒性和环境风险提供了关键的机制性见解.
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