人类转录因子足迹的全球参考映射
Jeff Vierstra1, John Lazar2,3, Richard Sandstrom2
1Altius Institute for Biomedical Sciences, Seattle, WA, USA. jvierstra@altius.org.
Nature
|July 31, 2020
概括
这项研究使用DNase I足迹绘制了人类基因组中的数百万个转录因子结合点. 这些调节足迹中的遗传变异对基因调节和人类特征产生重大影响.
科学领域:
- 基因组学
- 分子生物学
- 表观遗传学
背景情况:
- 与DNA结合的转录因子调节了基因表达.
- 调节DNA的遗传变异与疾病和特征有关.
- 识别功能性监管变体是一个挑战.
研究的目的:
- 在人类基因组中全面绘制转录因子足迹.
- 了解DNA可访问性和转录因子占用在基因调节中的作用.
- 研究遗传变异对监管要素的影响.
主要方法:
- 从243种人类细胞/组织类型中生成高密度DNase I分裂图.
- 整合数据以划分数百万个转录因子占用位点的核酸分辨率.
- 分析了遗传变异,足迹和监管元素的可访问性之间的关系.
主要成果:
- 在全基因组范围内划定了约450万个转录因子占用位.
- 发现cis调节主要由DNA可访问性调节,而不是差异性TF占用.
- 表明与疾病相关的变异在足迹中被丰富,具有几乎相同的功能损失/增益等位基因.
- 在足迹中发现了基因变异密度的增加,
结论:
- 提供转录因子结合位点的高分辨率地图.
- 提供分析基因调节机制和功能遗传变异的框架.
- 强调监管足迹对于理解人类疾病和进化的重要性.
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