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YY 1 regulates skeletal muscle regeneration through controlling metabolic reprogramming of satellite cells
Author(s) -
Chen Fengyuan,
Zhou Jiajian,
Li Yuying,
Zhao Yu,
Yuan Jie,
Cao Yang,
Wang Lijun,
Zhang Zongkang,
Zhang Baoting,
Wang Chi Chiu,
Cheung Tom H,
Wu Zhenguo,
Wong Carmen ChakLui,
Sun Hao,
Wang Huating
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201899727
Subject(s) - biology , skeletal muscle , microbiology and biotechnology , myogenesis , reprogramming , regeneration (biology) , myod , myocyte , cellular differentiation , stem cell , genetics , cell , anatomy , gene
Skeletal muscle satellite cells ( SC s) are adult muscle stem cells responsible for muscle regeneration after acute or chronic injuries. The lineage progression of quiescent SC toward activation, proliferation, and differentiation during the regeneration is orchestrated by cascades of transcription factors ( TF s). Here, we elucidate the function of TF Yin Yang1 ( YY 1) in muscle regeneration. Muscle‐specific deletion of YY 1 in embryonic muscle progenitors leads to severe deformity of diaphragm muscle formation, thus neonatal death. Inducible deletion of YY 1 in SC almost completely blocks the acute damage‐induced muscle repair and exacerbates the chronic injury‐induced dystrophic phenotype. Examination of SC revealed that YY 1 loss results in cell‐autonomous defect in activation and proliferation. Mechanistic search revealed that YY 1 binds and represses mitochondrial gene expression. Simultaneously, it also stabilizes Hif1α protein and activates Hif1α‐mediated glycolytic genes to facilitate a metabolic reprogramming toward glycolysis which is needed for SC proliferation. Altogether, our findings have identified YY 1 as a key regulator of SC metabolic reprogramming through its dual roles in modulating both mitochondrial and glycolytic pathways.