scholarly journals The Chromatin Remodeler Mi2/CHD4 is Required in Skeletal Muscle Stem Cells for Normal Muscle Development and Regeneration

Author(s):  
Assia Derfoul ◽  
Iago Pinal-Fernandez ◽  
Wilson Huang ◽  
Cassie Parks ◽  
Katherine Pak ◽  
...  

Abstract The chromodomain helicase and DNA binding 4 (CHD4) protein is upregulated in regenerating myofibers. To define the role of CHD4 in muscle differentiation and regeneration, we generated mice with CHD4 ablated in muscle satellite cells (SCs). Embryonic day 18.5 CHD4 KO mice are non-viable, with atrophic intercostal and back muscles and altered expression of muscle contraction genes. Tamoxifen-inducible conditional CHD4 KO in adult mouse SCs diminished myoblast proliferation, induced premature differentiation, and altered expression of muscle contraction genes at the myotube stage. Following cardiotoxin–induced muscle injury, CHD4 KO regenerating myofibers had reduced cross-sectional area. ChIP-Seq analysis revealed that CHD4 binds actin a1, Wnt and b-catenin genes, which are known to play roles in the regulation of myogenesis. Together, our results suggest an important role for CHD4 in the control of embryonic myogenesis, SC differentiation, and the control of muscle fiber size in adult skeletal muscle during regeneration.

Development ◽  
2012 ◽  
Vol 139 (12) ◽  
pp. e1208-e1208
Author(s):  
B. Gayraud-Morel ◽  
F. Chretien ◽  
A. Jory ◽  
R. Sambasivan ◽  
E. Negroni ◽  
...  

Author(s):  
Bingyuan Wang ◽  
Jiankang Guo ◽  
Mingrui Zhang ◽  
Zhiguo Liu ◽  
Rong Zhou ◽  
...  

Identifying the genes relevant for muscle development is pivotal to improve meat production and quality in pigs. Insulin-degrading enzyme (IDE), a thiol zinc-metalloendopeptidase, has been known to regulate the myogenic process of mouse and rat myoblast cell lines, while its myogenic role in pigs remained elusive. Therefore, the current study aimed to identify the effects of IDE on the proliferation and apoptosis of porcine skeletal muscle stem cells (PSMSCs) and underlying molecular mechanism. We found that IDE was widely expressed in porcine tissues, including kidney, lung, spleen, liver, heart, and skeletal muscle. Then, to explore the effects of IDE on the proliferation and apoptosis of PSMSCs, we subjected the cells to siRNA-mediated knockdown of IDE expression, which resulted in promoted cell proliferation and reduced apoptosis. As one of key transcription factors in myogenesis, MYOD, its expression was also decreased with IDE knockdown. To further elucidate the underlying molecular mechanism, RNA sequencing was performed. Among transcripts perturbed by the IDE knockdown after, a downregulated gene myostatin (MSTN) which is known as a negative regulator for muscle growth attracted our interest. Indeed, MSTN knockdown led to similar results as those of the IDE knockdown, with upregulation of cell cycle-related genes, downregulation of MYOD as well as apoptosis-related genes, and enhanced cell proliferation. Taken together, our findings suggest that IDE regulates the proliferation and apoptosis of PSMSCs via MSTN/MYOD pathway. Thus, we recruit IDE to the gene family of regulators for porcine skeletal muscle development and propose IDE as an example of gene to prioritize in order to improve pork production.


2022 ◽  
Vol 17 (1) ◽  
pp. 82-95
Author(s):  
Marina Arjona ◽  
Armon Goshayeshi ◽  
Cristina Rodriguez-Mateo ◽  
Jamie O. Brett ◽  
Pieter Both ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Rhianna C. Laker ◽  
James G. Ryall

An unresolved and critically important question in skeletal muscle biology is how muscle stem cells initiate and regulate the genetic program during muscle development. Epigenetic dynamics are essential for cellular development and organogenesis in early life and it is becoming increasingly clear that epigenetic remodeling may also be responsible for the cellular adaptations that occur in later life. DNA methylation of cytosine bases within CpG dinucleotide pairs is an important epigenetic modification that reduces gene expression when located within a promoter or enhancer region. Recent advances in the field suggest that epigenetic regulation is essential for skeletal muscle stem cell identity and subsequent cell development. This review summarizes what is currently known about how skeletal muscle stem cells regulate the myogenic program through DNA methylation, discusses a novel role for metabolism in this process, and addresses DNA methylation dynamics in adult skeletal muscle in response to physical activity.


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