title: Protein arginine methyltransferase 1 coactivates NF-kappaB-dependent gene expression synergistically with CARM1 and PARP1.
abstract: Nuclear factor kappa B (NF-kappaB) plays an important role in the transcriptional regulation of genes involved in inflammation and cell survival. Transcriptional coactivators that methylate histones become increasingly important. Recently, we provided evidence that coactivator-associated arginine methyltransferase 1 (CARM1) is a transcriptional coactivator of NF-kappaB and functions as a promoter-specific regulator of NF-kappaB recruitment to chromatin. Here, we show that protein arginine methyltransferase 1 (PRMT1) synergistically coactivates NF-kappaB-dependent gene expression at the macrophage inflammatory protein 2 and human immunodeficiency virus 1 long terminal repeat promoters in concert with the transcriptional coactivators p300/CREB binding protein, CARM1, and poly(ADP-ribose) polymerase 1. PRMT1 formed a complex with poly(ADP-ribose) polymerase 1 and NF-kappaB in vivo and interacted directly with the NF-kappaB subunit p65 in vitro. The methyltransferase activity of PRMT1 appeared essential for its coactivator function in context with CARM1 and p300/CREB binding protein. These results suggest that the cooperative action between PRMT1 and CARM1 is required for NF-kappaB-dependent gene expression.
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Paul O
authors.initials: PO
authors.lastname: Hassa
authors.forename: Marcela
authors.initials: M
authors.lastname: Covic
authors.forename: Mark T
authors.initials: MT
authors.lastname: Bedford
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hottiger
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000502:physiology; D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000235:genetics; D005786:Gene Expression Regulation; D016325:HIV Long Terminal Repeat / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; D016328:NF-kappa B; D015534:Trans-Activators; D051996:Transcription Factor RelA; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1; D050882:CREB-Binding Protein; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases