RASGRP1 targeted by H3K27me3 regulates myoblast proliferation and differentiation in mice and pigs

Acta Biochim Biophys Sin (Shanghai). 2024 Mar 25;56(3):452-461. doi: 10.3724/abbs.2024011.

Abstract

Skeletal muscle is not only the largest organ in the body that is responsible for locomotion and exercise but also crucial for maintaining the body's energy metabolism and endocrine secretion. The trimethylation of histone H3 lysine 27 (H3K27me3) is one of the most important histone modifications that participates in muscle development regulation by repressing the transcription of genes. Previous studies indicate that the RASGRP1 gene is regulated by H3K27me3 in embryonic muscle development in pigs, but its function and regulatory role in myogenesis are still unclear. In this study, we verify the crucial role of H3K27me3 in RASGRP1 regulation. The gain/loss function of RASGRP1 in myogenesis regulation is performed using mouse myoblast C2C12 cells and primarily isolated porcine skeletal muscle satellite cells (PSCs). The results of qPCR, western blot analysis, EdU staining, CCK-8 assay and immunofluorescence staining show that overexpression of RASGRP1 promotes cell proliferation and differentiation in both skeletal muscle cell models, while knockdown of RASGRP1 leads to the opposite results. These findings indicate that RASGRP1 plays an important regulatory role in myogenesis in both mice and pigs.

Keywords: H3K27me3; RASGRP1; cell proliferation; myoblasts; skeletal muscle.

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • Histones* / metabolism
  • Mice
  • Muscle, Skeletal / metabolism
  • Myoblasts* / metabolism
  • Swine

Substances

  • Histones
  • Guanine Nucleotide Exchange Factors

Grants and funding

This work was supported by the grants from the 2023 Key Areas Research and Development Programs - Modern Seed Industry of Guangdong Province, China (No. 2022B0202090002) and the Provincial Rural Revitalization Strategy Special Project on the Protection and Development and Utilization of Local Livestock and Poultry of Guangdong Province, China.