CARM1 activates myogenin gene via PCAF in the early differentiation of TPA-induced rhabdomyosarcoma-derived cells

J Cell Biochem. 2010 May;110(1):162-70. doi: 10.1002/jcb.22522.

Abstract

CARM1/PRMT4 is a member of the protein arginine methyltransferase (PRMT) family. CARM1 as a transcriptional coactivator plays an active role on mammalian genes. Here, we show that CARM1 can be recruited to the promoter of myogenin gene to enhance its transcriptional activation via PCAF at the early stage of TPA-induced RD cell differentiation. By adding adenosine dialdehyde, AdOx, to inhibit the PRMT in RD cells, the TPA-induced recruiting of p300, PCAF and the Brg1 at the myogenin promoter is abolished and myogenic differentiation is blocked. More specifically, the expression of PCAF and its nucleation are prohibited when CARM1 is knockdown by its specific siRNA. We suggest that the physical interaction of CARM1 and PCAF is likely pivotal for the activation of PCAF in the downstream of CARM1 pathway for inducing myogenin under TPA-induced differentiation. The findings shed lights on novel therapeutic targets in the treatment of rhabdomyosarcoma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Myogenin / genetics*
  • Myogenin / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Binding / drug effects
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Rhabdomyosarcoma / enzymology*
  • Rhabdomyosarcoma / genetics
  • Rhabdomyosarcoma / pathology
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Transcriptional Activation / drug effects*
  • p300-CBP Transcription Factors / genetics
  • p300-CBP Transcription Factors / metabolism*

Substances

  • Myogenin
  • periodate-oxidized adenosine
  • Protein-Arginine N-Methyltransferases
  • coactivator-associated arginine methyltransferase 1
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Adenosine
  • Tetradecanoylphorbol Acetate