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通过计算和 cis-eQTL 分析来表征ER应激反应调节的遗传变异

Nikki D Russell¹, Lynn B Jorde¹, Clement Y Chow¹

¹Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

G3 (Bethesda, Md.)

|October 4, 2023

概括

遗传变异通过改变转录因子结合来影响内质网膜 (ER) 应激反应. 这项研究确定了影响ER压力基因表达的特定遗传变异 (cis-eQTLs),解释了反应变异性.

科学领域:

基因组学就是基因组学.
分子生物学分子生物学
系统生物学系统生物学

背景情况:

错误折叠的蛋白质触发了内质网膜 (ER) 应激反应,这是一个由三个关键转录因子 (TF) 调节的转录程序:XBP1,ATF6和ATF4.
遗传变异有助于ER应激反应的变化,可能是通过TF结合和活性的修改.

研究的目的:

通过改变转录因子结合,研究遗传变异如何影响ER应激反应.
在人类样本中识别与ER应激反应变异性相关的cis-eQTL.

主要方法:

开发了一个计算管道来识别人类基因组中的潜在TF结合位点 (TFBS).
利用GTEx数据在预测的TFBS中找到cis-eQTL.
分析了ClinVar数据库,用于TF结合基因中的变异性致病性.
在ER压力下对人类细胞系进行cis-eQTL分析.

主要成果:

确定了特定条件的cis-eQTLs (控制与ER压力).
发现一些压力特定的cis-eQTL位于关键ER压力TF的TFBS内.
在ER应激过程中通过改变的TF结合,观察到cis-eQTLs影响基因表达的潜在机制.

结论:

本研究介绍了首次对经历ER压力的人类样本进行cis-eQTL分析.
在TFBS中确定了特定条件的cis-eQTL,为ER应激反应变化提供了机制解释.
这项工作对于精确定位基因因素,即不同ER应激反应背后的基因因素至关重要.

关键词:

在 cis-eQTL 中.压力ERER压力ERER压力遗传资源是一种遗传资源.遗传变异是一种遗传变异.转录变异性的变化.

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