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Direct and Specific Functional Evaluation of the Nrf2 and MafG Heterodimer by Introducing a Tethered Dimer into Small

Fumiki Katsuoka1, Akihito Otsuki2, Mizue Takahashi2

  • 1Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan kfumiki@med.tohoku.ac.jp masiyamamoto@med.tohoku.ac.jp.

Molecular and Cellular Biology
|August 7, 2019
PubMed

Insights

The Nrf2-MafG heterodimer directly activates Nrf2-dependent genes. This study developed a novel assay system to specifically evaluate CNC-sMaf heterodimer function in cytoprotection.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Transcription Factors

Background:

  • Cytoprotective genes are regulated by cap'n'collar (CNC) and small Maf (sMaf) protein heterodimers.
  • The precise function of specific Nrf2-sMaf heterodimers requires direct evaluation.

Purpose of the Study:

  • To specifically assess the transcriptional activity of the Nrf2-MafG heterodimer.
  • To develop a novel assay system for evaluating CNC-sMaf heterodimer function.

Main Methods:

  • Constructed a tethered Nrf2-MafG (T-N2G) heterodimer.
  • Introduced the T-N2G construct into sMaf-deficient cells.
  • Utilized diethyl maleate as an Nrf2 activator.
  • Performed genome-wide binding analysis.

Main Results:

  • The T-N2G heterodimer activated Nrf2 target genes but not Nrf1 target genes.
  • T-N2G preferentially bound to CNC-sMaf binding elements (CsMBE) in Nrf2 target gene regulatory regions.
  • Demonstrated direct evidence for Nrf2-MafG acting as a transcriptional activator.

Conclusions:

  • The Nrf2-MafG heterodimer is a key transcriptional activator of Nrf2-dependent genes.
  • The developed assay system enables specific examination of various CNC-sMaf heterodimers.
  • This research provides direct evidence for the role of Nrf2-MafG in gene regulation.
Keywords:
CsMBENrf2small Maftethered moleculetranscription factor

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