人类基因组中的DNA甲基化-环境相互作用
Rachel A Johnston1,2,3, Katherine A Aracena4, Luis B Barreiro4,5,6
1Department of Evolutionary Anthropology, Duke University, Durham, NC 27708, USA.
bioRxiv : the preprint server for biology
|June 9, 2023
概括
DNA甲基化模式影响基因调节和细胞对干扰素α等环境因素的反应. 这项研究使用mSTARR-seq来绘制人类基因组中的这些相互作用.
科学领域:
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 基因甲基化是影响基因调节的关键表观遗传机制.
- 了解DNA甲基化如何与环境因素相互作用,对于破译细胞反应至关重要.
- 以前的方法允许测试数百万个位点,但缺乏全面的基因组覆盖.
研究的目的:
- 通过使用mSTARR-seq.q.全面地绘制全基因组增强剂活性和DNA甲基化依赖的调节功能.
- 研究DNA甲基化如何影响细胞对环境刺激的反应,例如干扰素α (IFNA).
- 探索DNA甲基化,环境暴露和基因调节之间的联系.
主要方法:
- 应用mSTARR-seq来查询几乎整个人类基因组,重点关注CPG位点.
- 使用Illumina Infinium MethylationEPIC阵列和减少表示双硫酸盐测序,对CpG位点进行分析.
- 评估对IFNA刺激的调节反应,并预测人类巨细胞对流感病毒的转录反应.
主要成果:
- 含有CpG位点的基因组片段被丰富为调控能力.
- 取决于DNA甲基化的调节活动对细胞环境敏感,特别是减弱IFNA反应.
- 甲基化依赖的IFNA反应预测了对流感病毒的甲基化依赖的转录反应.
结论:
- 预先存在的DNA甲基化模式可以影响对后续环境暴露的反应,支持生物嵌入.
- 发现了广泛的DNA甲基化环境相互作用.
- 在与早期生命逆境相关的部位对基因调节的功能影响中没有发现显著的丰富.
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