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Status |
Public on Apr 09, 2019 |
Title |
YY1 regulates skeletal muscle regeneration through controlling metabolic reprogramming during adult muscle stem cell activation |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Skeletal muscle satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute or chronic injuries. The lineage progression of quiescent satellite cells toward activation, proliferation and differentiation during the regeneration is orchestrated by cascades of transcription factors (TFs). Here we elucidate the functional role of a ubiquitously expressed TF, Yin Yang1 (YY1) in muscle regeneration. Muscle-specific deletion of YY1 in embryonic muscle progenitors leads to severe deformity of diaphragm muscle formation thus postnatal death. Inducible deletion of YY1 in satellite cells almost completely blocks the acute damage induced muscle repair and exacerbates the chronic injury induced dystrophic phenotype. Examination of SCs revealed that YY1 loss results in cell autonomous defect in cell activation and proliferation. Mechanistic search through genome-wide profiling of YY1 regulated transcriptome and YY1 binding revealed that YY1 binds and suppresses mitochondrial gene expression. Simultaneously, it also activates Hif1α mediated glycolytic genes to facilitate a metabolic reprogramming toward glycolysis which is needed for SC activation. Altogether our findings have identified YY1 as a key regulator of SC metabolic reprogramming during cell activation through its dual roles in modulating both mitochondrial and glycolytic pathways.
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Overall design |
2 ChIP-seq and 4 RNA-seq experiments were performed
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Contributor(s) |
Wang H, Sun H, Chen F, Zhou J |
Citation(s) |
30979776 |
Submission date |
Dec 18, 2017 |
Last update date |
Jul 09, 2019 |
Contact name |
Jiajian Zhou |
E-mail(s) |
zhoujj2013@gmail.com
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Organization name |
Southern Medical University
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Department |
Dermatology Hospital
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Street address |
No. 2 Lujing Road, Yuexiu District,
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City |
Guangzhou |
State/province |
Guangdong |
ZIP/Postal code |
NA |
Country |
China |
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Platforms (2) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
GPL15103 |
Illumina HiSeq 1000 (Mus musculus) |
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Samples (6)
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Relations |
BioProject |
PRJNA422919 |
SRA |
SRP126976 |