通过OG-Seq测序小鼠基因组的氧化修饰基 8-Oxo-7,8-二
Yun Ding1, Aaron M Fleming1, Cynthia J Burrows1
1Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
Journal of the American Chemical Society
|February 3, 2017
概括
氧化损伤会在DNA中产生8-oxo-7,8-dihydroguanine (OG),特别是在5'-GG-3'位点. 新的测序方法揭示了基因调节区域的OG丰富,影响了基因表达和疾病.
科学领域:
- 基因组学
- 分子生物学
- DNA 修复
背景情况:
- 氧化应激会导致DNA损伤,形成8-oxo-7,8-二氨酸 (OG).
- 在体外研究表明,在暴露于活性氧物种时,5 - GG-3序列中的OG形成偏好.
- 遗传基因的基因组分布和生物相关性尚不完全理解.
研究的目的:
- 使用一种新奇的测序技术绘制OG病变的基因组位置.
- 研究Ogg1DNA修复酶对OG分布的影响.
- 确定OG丰富是否与特定的基因组特征相关,如基因促进物和UTR.
主要方法:
- 开发和应用"OG-Seq",一种用于绘制OG地点的下一代测序方法.
- 在野生型 (WT) 小鼠胚胎纤维细胞中分析OG分布.
- 在WT细胞中的OG分布与缺乏Ogg1修复酶的细胞的比较.
主要成果:
- 在WT小鼠胚胎纤维细胞中确定了大约10,000个OG丰富区域.
- 在Ogg1淘汰细胞中观察到大约18,000个OG丰富区域,表明Ogg1在修复中的作用.
- 在基因促进物和未翻译区域 (UTR) 中发现了显著的OG位点丰富,特别是在5-GG-3环境中.
结论:
- 该研究通过在体内证明5 -GG-3位点的偏好性OG形成来验证体内发现.
- OG-Seq为研究DNA基因修饰及其基因组影响提供了强大的工具.
- 在调节区域内OG的局部化表明在基因调节和疾病相关突变中的潜在作用.
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