Protein Arginine Methyltransferase 1 Coactivates NF-κB-Dependent Gene Expression Synergistically with CARM1 and PARP1

Nuclear factor kappa B (NF-κB) 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-κB and functions as a promoter-specific regulator of NF-κB recruitment to chromatin. Here, we show that protein arginine methyltransferase 1 (PRMT1) synergistically coactivates NF-κB-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-κB in vivo and interacted directly with the NF-κB 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-κB-dependent gene expression.