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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE134353 | GEO | 2019/08/06

REPOSITORIES: GEO

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Direct and Specific Functional Evaluation of the Nrf2 and MafG Heterodimer by Introducing a Tethered Dimer into Small Maf-Deficient Cells.

Project description:A group of cytoprotective genes is regulated by heterodimers composed of the cap'n'collar (CNC) family member Nrf2 and one of the small Maf (sMaf) proteins (MafF, MafG, or MafK) through the antioxidant response element (ARE, also referred to as the CNC-sMaf binding element [CsMBE]). Many lines of evidence support this model; however, a direct and specific evaluation of the Nrf2-sMaf heterodimer remains to be executed. To address this issue, we constructed a tethered Nrf2-MafG (T-N2G) heterodimer using a flexible linker peptide. We then introduced the T-N2G construct into cells lacking all three sMaf proteins to specifically evaluate the function of the tethered heterodimer without interference from other endogenous CNC-sMaf heterodimers or sMaf homodimers. In response to an Nrf2 activator, diethyl maleate, the T-N2G protein can widely activate the target genes of Nrf2 but not those of Nrf1, such as proteasome subunit genes. Genome-wide binding analysis showed that the T-N2G protein preferentially bound to the CsMBE motifs in the regulatory regions of the Nrf2 target genes. These results provide direct evidence that the Nrf2-MafG heterodimer acts as a transcriptional activator of Nrf2-dependent genes and show that this assay system will be a powerful tool to specifically examine the function of other CNC-sMaf heterodimers.

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

Project description:Direct and Specific Functional Evaluation of the Nrf2 and MafG Heterodimer by Introducing a Tethered Dimer into Small Maf-Deficient Cells

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Gene expression profile in the tethered Nrf2-MafG (T-N2G) heterodimer-expressing small Maf-deficient cells [RNA-seq]

Project description:To elucidate the function of Nrf2-small Maf heterodimer, we constructed a tethered Nrf2-MafG (T-N2G) heterodimer using a flexible linker peptide and examined its function in the small Maf-deficient mouse embryonic fibroblast (MEF).

2019-08-06 | GSE134351 | GEO

Gene expression profile in the tethered Nrf1-MafG (T-N1G) heterodimer-expressing small Maf-deficient cells [RNA-seq]

Project description:To elucidate the function of Nrf1-small Maf heterodimer, we constructed a tethered Nrf1-MafG (T-N1G) heterodimer using a flexible linker peptide and examined its function in the small Maf-deficient mouse embryonic fibroblast (MEF).

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Genome wide-binding profile of tethered Nrf2-MafG (T-N2G) heterodimers in the small Maf-deficient cells [ChIP-seq]

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Gene expression profile in the tethered Nrf2-MafG (T-N2G) heterodimer-expressing small Maf-deficient cells [RNA-seq]

Project description:Gene expression profile in the tethered Nrf2-MafG (T-N2G) heterodimer-expressing small Maf-deficient cells [RNA-seq]

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Target Gene Diversity of the Nrf1-MafG Transcription Factor Revealed by a Tethered Heterodimer

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-01-30 | GSE188788 | GEO

Genome wide-binding profile of tethered Nrf1-MafG (T-N1G) heterodimers in the small Maf-deficient cells [ChIP-seq]

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Small Maf proteins (MafF, MafG, MafK): History, structure and function.

Project description:The small Maf proteins (sMafs) are basic region leucine zipper (bZIP)-type transcription factors. The basic region of the Maf family is unique among the bZIP factors, and it contributes to the distinct DNA-binding mode of this class of proteins. MafF, MafG and MafK are the three vertebrate sMafs, and no functional differences have been observed among them in terms of their bZIP structures. sMafs form homodimers by themselves, and they form heterodimers with cap 'n' collar (CNC) proteins (p45 NF-E2, Nrf1, Nrf2, and Nrf3) and also with Bach proteins (Bach1 and Bach2). Because CNC and Bach proteins cannot bind to DNA as monomers, sMafs are indispensable partners that are required by CNC and Bach proteins to exert their functions. sMafs lack the transcriptional activation domain; hence, their homodimers act as transcriptional repressors. In contrast, sMafs participate in transcriptional activation or repression depending on their heterodimeric partner molecules and context. Mouse genetic analyses have revealed that various biological pathways are under the regulation of CNC-sMaf heterodimers. In this review, we summarize the history and current progress of sMaf studies in relation to their partners.

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Gene expression profile in the tethered Nrf1-MafG (T-N1G) heterodimer-expressing small Maf-deficient cells [RNA-seq]

Project description:Gene expression profile in the tethered Nrf1-MafG (T-N1G) heterodimer-expressing small Maf-deficient cells [RNA-seq]

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