Myostatin Mutation Enhances Bovine Myogenic Differentiation through PI3K/AKT/mTOR Signalling via Removing DNA Methylation of RACK1

Cells. 2022 Dec 23;12(1):59. doi: 10.3390/cells12010059.

Abstract

Myostatin (MSTN) is a negative regulator of skeletal muscle development and plays an important role in muscle development. Fluctuations in gene expression influenced by DNA methylation are critical for homeostatic responses in muscle. However, little is known about the mechanisms underlying this fluctuation regulation and myogenic differentiation of skeletal muscle. Here we report a genome-wide analysis of DNA methylation dynamics in bovine skeletal muscle myogenesis after myostatin editing. We show that, after myostatin editing, an increase in TETs (DNA demethylases) and a concomitant increase in the receptor for activated C kinase 1 (RACK1) control the myogenic development of skeletal muscle. Interestingly, enhancement of PI3K/AKT/mTOR signaling by RACK1 appears to be an essential driver of myogenic differentiation, as it was associated with an increase in myogenic differentiation marker factors (MyHC and MyoG) during muscle differentiation. Overall, our results suggest that loss of myostatin promotes the myogenic differentiation response in skeletal muscle by decreasing DNA methylation of RACK1.

Keywords: DNA methylation; PI3K/AKT/mTOR signaling; RACK1; myogenic differentiation; myostatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • DNA Methylation / genetics
  • Muscle Development / genetics
  • Myostatin / genetics
  • Myostatin / metabolism
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Myostatin
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Protein-Tyrosine Kinases

Grants and funding

This work was supported by the Natural Science Foundation of Tianjin (grant numbers: 20JCQNJC00640) and the National Transgenic Animal Program (grant numbers: 2016ZX08007-002).