Defining the Functional Targets of Cap'n'collar Transcription Factors NRF1, NRF2, and NRF3.

The NRF transcription factors NRF1, NRF2, and NRF3, are a subset of Cap'n'collar transcriptional regulators which modulate the expression of genes harboring antioxidant-response element (ARE) sequences within their genomic loci. Despite the emerging physiological importance of NRF family members, the repertoire of their genetic targets remains incompletely defined. Here we use RNA-sequencing-based transcriptional profiling and quantitative proteomics to delineate the overlapping and differential genetic programs effected by the three NRF transcription factors. Comparing our data to recent profiling analyses, we create consensus target gene sets regulated by NRF1, NRF2, and NRF3, genetic programs which we determine to be differentially regulated in human tissues. Together, our data provide a quantitative assessment of how NRF family members sculpt proteomes and transcriptomes, essential information for future studies evaluating the role of NRF factors in normal physiology and disease. Overall design: Comparisons of the transcriptomes of HEK293T cells expressing empty vector, FLAG-NRF1, FLAG-NRF2(T80D), or FLAG-NRF3.

核因子红细胞2相关因子（Nuclear factor erythroid 2-related factor, NRF）转录因子家族的NRF1、NRF2与NRF3，属于帽领转录调节因子（Cap'n'collar）的一个亚类，可调控基因组位点内携带有抗氧化反应元件（antioxidant-response element, ARE）序列的基因的表达。尽管NRF家族成员的生理学重要性日益凸显，但其遗传靶标的完整集合仍未被完全阐明。本研究采用基于RNA测序的转录组分析与定量蛋白质组学技术，阐明三类NRF转录因子所介导的重叠与差异化遗传调控程序。通过将本研究数据与近期相关转录组分析结果进行比对，我们构建了由NRF1、NRF2及NRF3调控的共识靶基因集，并证实该类遗传调控程序在人体组织中呈现差异化调控特征。综上，本研究对NRF家族成员如何塑造细胞蛋白质组与转录组进行了定量评估，相关结果可为后续解析NRF因子在正常生理活动与疾病进程中的作用提供关键依据。实验设计概述：对表达空载体、FLAG-NRF1、FLAG-NRF2(T80D)或FLAG-NRF3的HEK293T细胞的转录组进行比较分析。