Genomics

Dataset Information

297

Nrf2 bindng in C2C12 myotubes


ABSTRACT: Nrf2 (NF-E2-related-factor-2) contributes to the maintenance of glucose homeostasis in vivo. Nrf2 suppresses blood glucose levels by protecting pancreatic β-cells from oxidative stress and improving peripheral tissue glucose utilization. To elucidate the molecular mechanisms by which Nrf2 contributes to the maintenance of glucose homeostasis, we generated skeletal muscle (SkM)-specific Keap1-knockout (Keap1MuKO) mice that express abundant Nrf2 in SkM and then examined Nrf2-target gene expression in this tissue. In Keap1MuKO mice, blood glucose levels were significantly downregulated, and the levels of glycogen branching enzyme (Gbe1) mRNA, along with those of glycogen branching enzyme (GBE) protein, were significantly upregulated in mouse SkM. Consistent with this result, chemical Nrf2-inducers promoted Gbe1 mRNA expression in both mouse SkM and C2C12 myotubes. Chromatin-immunoprecipitation analysis demonstrated that Nrf2 binds the Gbe1 upstream promoter regions. In Keap1MuKO mice, muscle glycogen content was strongly reduced, and forced GBE expression in C2C12 myotubes promoted glucose uptake. Therefore, our results demonstrate that Nrf2-induction in SkM increases GBE expression and reduces muscle glycogen content, resulting in improved glucose tolerance. Chromatin occupancy of Nrf2 under CDDO-Im-treated condition were generated by deep sequencing, in dupliplicate

ORGANISM(S): Mus musculus  

SUBMITTER: Akira Uruno   Yoko Yagishita  Fumiki Katsuoka  Masayuki Yamamoto 

PROVIDER: E-GEOD-78780 | ArrayExpress | 2016-04-06

SECONDARY ACCESSION(S): SRP070990GSE78780PRJNA313517

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Nrf2-Mediated Regulation of Skeletal Muscle Glycogen Metabolism.

Uruno Akira A   Yagishita Yoko Y   Katsuoka Fumiki F   Kitajima Yasuo Y   Nunomiya Aki A   Nagatomi Ryoichi R   Pi Jingbo J   Biswal Shyam S SS   Yamamoto Masayuki M  

Molecular and cellular biology 20160516 11


Nrf2 (NF-E2-related factor 2) contributes to the maintenance of glucose homeostasis in vivo Nrf2 suppresses blood glucose levels by protecting pancreatic β cells from oxidative stress and improving peripheral tissue glucose utilization. To elucidate the molecular mechanisms by which Nrf2 contributes to the maintenance of glucose homeostasis, we generated skeletal muscle (SkM)-specific Keap1 knockout (Keap1MuKO) mice that express abundant Nrf2 in their SkM and then examined Nrf2 target gene expre  ...[more]

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