转录因子结合区域的DNA甲基化模式标志着它们的功能和进化背景
Martina Rimoldi1, Ning Wang2, Jilin Zhang2
1European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
Genome biology
|June 6, 2024
概括
转录因子结合部位的DNA甲基化模式在哺乳动物中得到保存,并随着TF占用而演变. 这些表观遗传标记揭示了不同的调节功能和色素格局.
科学领域:
- 表观遗传学和基因组学
- 进化生物学 进化生物学
- 哺乳动物分子生物学
背景情况:
- 基因组甲基化是影响基因组功能的关键表观遗传修饰,在转录因子 (TF) 结合部位和抑制区域观察到不同的模式.
- 建立全基因组和TF结合点甲基化模式的机制仍然不完全理解.
研究的目的:
- 为了研究DNA甲基化和TF结合进化在哺乳动物物种之间的关联.
- 确定TF结合区域的保存DNA甲基化模式及其功能影响.
主要方法:
- 在五种哺乳动物物种 (人,,老鼠,老鼠,狗) 的肝脏中对DNA甲基化进行比较的表观基因组分析.
- 将DNA甲基化数据与五个不同的TF (CTCF,CEBPA,HNF4A,ONECUT1,FOXA1) 的已发布占用概况集成.
- 应用分类和聚类方法来识别TF绑定区域的保存甲基化模式.
主要成果:
- TF结合部位表现出低或中等的DNA甲基化水平,受周围区域的甲基化影响.
- 在TF结合区域确定了独特的,物种保留的DNA甲基化模式,四个TF共享模式,CTCF不同.
- 在TF占用率的进化损失后观察到DNA甲基化增加,这表明甲基化和TF结合之间的协调进化.
结论:
- 特定的DNA甲基化配置文件标志着TF结合,与调节活性相关,染色质背景和进化轨迹.
- 表观基因组分析揭示了DNA甲基化在调解跨物种TF结合变化的作用.
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