Transcription factor EGR1 promotes differentiation of bovine skeletal muscle satellite cells by regulating MyoG gene expression

J Cell Physiol. 2018 Jan;233(1):350-362. doi: 10.1002/jcp.25883. Epub 2017 May 18.

Abstract

The transcription factor, early growth response 1 (EGR1), has important roles in various cell types in response to different stimuli. EGR1 is thought to be involved in differentiation of bovine skeletal muscle-derived satellite cells (MDSCs); however, the precise effects of EGR1 on differentiation of MDSCs and its mechanism of action remain unknown. In the present study, a time course of EGR1 expression and the effects of EGR1 on MDSC differentiation were determined. The results demonstrated that the expression of EGR1 mRNA and protein increased significantly in differentiating MDSCs relative to that in proliferating cells. Over-expression of the EGR1 gene in MDSCs promoted their differentiation and inhibited proliferation. Conversely, knock-down of EGR1 inhibited differentiation of MDSCs and promoted their proliferation, indicating that EGR1 promotes MDSC differentiation. Moreover, over-expression of EGR1 in MDSCs increased the expression of MyoG mRNA and protein, whereas its knock-down had the opposite effect. Furthermore, ChIP-PCR analyses demonstrated that EGR1 could bind directly to its putative binding site within the promoter region of MyoG, and determination of ERG1 subcellular localization in MDSCs demonstrated that it could relocate to the nucleus, indicating MyoG is likely an EGR1 target gene whose expression is positively regulated by this transcription factor. In conclusion, EGR1 can promote MDSC differentiation through positive regulation of MyoG gene expression.

Keywords: EGR1; MyoG; bovine skeletal muscle satellite cells; differentiation.

MeSH terms

  • Animals
  • Binding Sites
  • CRISPR-Cas Systems
  • Cattle
  • Cell Differentiation*
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Computational Biology
  • Databases, Genetic
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism*
  • Gene Expression Regulation, Developmental
  • Muscle Development*
  • Myogenin / genetics
  • Myogenin / metabolism*
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Satellite Cells, Skeletal Muscle / metabolism*
  • Signal Transduction
  • Time Factors
  • Transfection

Substances

  • Early Growth Response Protein 1
  • Myogenin
  • RNA, Messenger