人类基因为中心的转录因子网络用于增强剂和疾病变异
Juan I Fuxman Bass1, Nidhi Sahni2, Shaleen Shrestha1
1Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cell
|April 25, 2015
概括
这项研究引入了一种新的方法,通过测试与疾病突变结合的转录因子 (TF) 来绘制人类基因调节网络 (GRNs) 的地图. 这种方法确定了突变如何改变TF相互作用,影响基因表达和疾病.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 基因调节网络 (GRNs) 对发育和生理学至关重要,涉及转录因子 (TF) 和调节性DNA元素之间的相互作用.
- 大多数与疾病相关的突变发生在非编码区域,但目前的GRN映射方法无法同时评估TF对正常和突变DNA的结合.
研究的目的:
- 开发和验证一种高通量方法,用于绘制人类GRNs,并描述非编码突变对TF结合的影响.
- 确定与野生类型和突变性调节基点结合的转录因子.
主要方法:
- 利用基因中心酵母单杂交 (eY1H) 试验来测试1086个人类TFs与246个增强剂和109个非编码疾病突变的结合.
- 与野生类型增强剂相比,评估了与突变位点的TF相互作用变化.
主要成果:
- 检测到TF与突变局部相互作用的损失和收益.
- 观察到TF与突变基因位点结合的变化与目标基因表达的变化一致.
- 证明了YY1H试验对于高通量变体表征的实用性.
结论:
- 已建立的YY1H测定作为绘制人类GRNs的强大工具.
- 展示了YY1H试验对基因组变异的高通量表征的能力,包括通过全基因组关联研究 (GWAS) 识别的非编码疾病突变.
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