PRMT1 activates myogenin transcription via MyoD arginine methylation at R121

Biochim Biophys Acta Gene Regul Mech. 2019 Oct;1862(10):194442. doi: 10.1016/j.bbagrm.2019.194442. Epub 2019 Oct 18.

Abstract

MyoD is a determining transcription factor involved in myogenic cell differentiation. Post translational modifications of MyoD, including phosphorylation and acetylation, can regulate its transcription activity. Inhibition of protein arginine methyltransferase 1 (PRMT1) leads to insufficient muscle differentiation. However, little is known about arginine methylation in regulating MyoD activity. Here, we demonstrated that MyoD interacts with PRMT1 via its bHLH domain. MyoD could be methylated by PRMT1 at R121. Moreover, R111 and R121 of MyoD are responsible for MyoD-mediated myogenin gene transcription in C2C12 cells. PRMT1 promotes MyoD-mediated myogenin expression, for which the enzymatic activity of PRMT1 is needed. The arginine methylation of MyoD by PRMT1 enhances its DNA binding activity and transactivation. Our data help to further clarify the molecular mechanism of PRMT1 in regulating muscle cell differentiation and provide a new therapeutic target for diseases caused by the abnormal differentiation of muscle cells.

Keywords: Arginine methylation; MyoD; Myogenin; PRMT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / genetics
  • Cell Differentiation / genetics
  • Gene Expression Regulation / genetics
  • Humans
  • Methylation
  • Muscle Development / genetics
  • MyoD Protein / genetics*
  • Myogenin / genetics*
  • Protein Processing, Post-Translational / genetics
  • Protein-Arginine N-Methyltransferases / genetics*
  • Repressor Proteins / genetics*
  • Transcription, Genetic*

Substances

  • MyoD Protein
  • Myogenin
  • Repressor Proteins
  • Arginine
  • PRMT1 protein, human
  • Protein-Arginine N-Methyltransferases