title: Co-operation between protein-acetylating and protein-methylating co-activators in transcriptional activation.
abstract: 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.
authors.affiliation: Department of Pathology, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90089, USA. stallcup@hsc.usc.edu
authors.forename: M R
authors.initials: MR
authors.lastname: Stallcup
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: S S
authors.initials: SS
authors.lastname: Koh
authors.forename: H
authors.initials: H
authors.lastname: Ma
authors.forename: Y H
authors.initials: YH
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: B T
authors.initials: BT
authors.lastname: Schurter
authors.forename: D W
authors.initials: DW
authors.lastname: Aswad
mesh_terms: D000107:Acetylation; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D017930:Genes, Reporter; D006657:Histones / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D002843:Chromatin; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D001120:Arginine; D008780:Methyltransferases; C077013:PRMT2 protein, human; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1