Co-operation between protein-acetylating and protein-methylating co-activators in transcriptional activation

Biochem Soc Trans. 2000;28(4):415-8.


Nuclear hormone receptors (NRs) activate transcription by binding to specific enhancer elements associated with target genes. Transcriptional activation is accomplished with the help of complexes of co-activator proteins that bind to NRs. p160 co-activators, a family of three related 160 kDa proteins, serve as primary co-activators by binding directly to NRs and recruiting additional secondary co-activators. Some of these (CBP/p300 and p/CAF) can acetylate histones and other proteins in the transcription complex, thus helping to modify chromatin structure and form an active transcription initiation complex. We recently discovered co-activator-associated arginine methyltransferase 1 (CARM1), which binds to p160 co-activators and thereby enhances transcriptional activation by NRs on transiently transfected reporter genes. CARM1 also methylates specific arginine residues in the N-terminal tail of histone H3 in vitro. A related arginine-specific protein methyltransferase, PRMT1, also binds p160 co-activators and enhances NR function. PRMT1 methylates histone H4 in vitro. The enhancement of NR function by CARM1, PRMT1 and p300 depends on their interactions with p160 co-activators. In the presence of p160 co-activators, some pairs of these three secondary co-activators provide a highly synergistic enhancement of NR function on transiently transfected reporter genes. We have also observed an enhancement of NR function on stably integrated reporter genes by these co-activators. We propose that the synergy of co-activator function between p300, CARM1 and PRMT1 is due to their different but complementary protein modification activities.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Animals
  • Arginine / metabolism
  • Cell Line
  • Cell Nucleus / metabolism*
  • Chromatin / metabolism
  • Enhancer Elements, Genetic
  • Genes, Reporter
  • Histones / metabolism*
  • Intracellular Signaling Peptides and Proteins
  • Methylation
  • Methyltransferases / metabolism
  • Nuclear Proteins / metabolism
  • Protein-Arginine N-Methyltransferases / metabolism
  • Recombinant Proteins / metabolism
  • Trans-Activators / metabolism
  • Transcription, Genetic
  • Transcriptional Activation*
  • Transfection


  • Chromatin
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Recombinant Proteins
  • Trans-Activators
  • Arginine
  • Methyltransferases
  • PRMT2 protein, human
  • Protein-Arginine N-Methyltransferases
  • coactivator-associated arginine methyltransferase 1