Distinct isoforms of Nrf1 diversely regulate different subsets of its cognate target genes

Scientific Reports
Meng WangYiguo Zhang

Abstract

The single Nrf1 gene has capability to be differentially transcripted alongside with alternative mRNA-splicing and subsequent translation through different initiation signals so as to yield distinct lengths of polypeptide isoforms. Amongst them, three of the most representatives are Nrf1α, Nrf1β and Nrf1γ, but the putative specific contribution of each isoform to regulating ARE-driven target genes remains unknown. To address this, we have herein established three cell lines on the base of the Flp-In T-REx system, which are allowed for the tetracycline-inducibly stable expression of Nrf1α, Nrf1β and Nrf1γ. Consequently, the RNA-Sequencing results have demonstrated that a vast majority of differentially expressed genes (i.e. >90% DEGs detected) were dominantly up-regulated by Nrf1α and/or Nrf1β following induction by tetracycline. By contrast, the other DEGs regulated by Nrf1γ were far less than those regulated by Nrf1α/β (i.e. ~11% of Nrf1α and ~7% of Nrf1β). However, further transcriptomic analysis revealed that the tetracycline-induced expression of Nrf1γ significantly increased the percentage of down-regulated genes in total DEGs. These statistical data were further validated by quantitative real-time PCR. The experimental re...Continue Reading

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Citations

Oct 20, 2019·The Journal of Biological Chemistry·Pengfei LiuAikseng Ooi
May 28, 2020·International Journal of Molecular Sciences·Jun Hamazaki, Shigeo Murata
Feb 1, 2020·Trends in Biochemical Sciences·Annelies BogaertKris Gevaert

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Methods Mentioned

BETA
PCR
RNA-Seq
Protein Assay

Software Mentioned

Stat
STRING
SOAP2
BioGRID
PossionDis
DAVID
Cytoscape

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