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Updated: Jul 15, 2025

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Published on: January 20, 2016

通过使用大规模的ChIP-Seq数据,通过表观遗传景观来阐明污染物引发的与疾病相关的机制

Zhaonan Zou¹, Yuka Yoshimura¹, Yoshihiro Yamanishi²

¹Department of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan.

Epigenetics & chromatin

|September 24, 2023

概括

环境污染物环境污染物

科学领域:

环境表观遗传学环境表观遗传学
毒素基因组学毒素基因组学
计算生物学是一种计算生物学.

背景情况:

环境污染物对人类健康的影响已知,但其作用模式尚不清楚.
基于转录基因组的方法可以预测化学疾病的联系,但缺乏对基因表达调节的洞察力.
了解污染物诱导的基因表达变化对于公共卫生至关重要.

研究的目的:

开发一种数据挖掘方法,DAR-ChIPEA,用于识别涉及污染物作用模式的转录因子 (TF).
阐明污染物毒性背后的表观遗传机制.
预测环境污染物引发的与疾病相关的机制.

主要方法:

利用大规模的ChIP-Seq数据 (人类和老鼠) 来预测富含污染物诱导的差异可访问基因组区域 (DAR) 的TF.
综合表观基因组 (ATAC-Seq) 和TF-疾病关联数据以推断污染物作用模式.
根据化学扰动数据集和先前开发的DEG-ChIPEA方法验证了DAR-ChIPEA.

主要成果:

在预测污染物-TF关联方面,DAR-ChIPEA显著优于DEG-ChIPEA (AUC得分:0.7287比0.7060).
确定了特定的TF驱动的污染物毒性机制,包括因微酸引起的过敏和PM2.5介导的免疫功能障碍.
通过破坏脂质新陈代谢和昼夜节律,证明了诱导的脂肪肝.

结论:

与基因相邻域分析相比,专注于全基因组的染色质变化为污染物反应提供了更好的洞察力.
在DAR-ChIPEA方法可以识别关键的TFs调解污染物效应.
这种方法有助于制定减轻环境污染损害的战略.

关键词:

在ATAC-seqq中使用.环境污染物的作用模式这就是ChIP-Seq.不同可访问的基因组区域.表观遗传的景观是表观遗传的.转录因子是一种转录因子.

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Epigenetic Regulation

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...

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Chromatin Immunoprecipitation- ChIP

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