Hassa Paul O, Covic Marcela, Bedford Mark T, Hottiger Michael O
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
J Mol Biol. 2008 Mar 28;377(3):668-78. doi: 10.1016/j.jmb.2008.01.044. Epub 2008 Jan 26.
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.
核因子κB（NF-κB）在参与炎症和细胞存活的基因转录调控中发挥重要作用。使组蛋白甲基化的转录共激活因子变得越来越重要。最近，我们提供了证据表明共激活因子相关精氨酸甲基转移酶1（CARM1）是NF-κB的转录共激活因子，并作为NF-κB募集到染色质的启动子特异性调节因子发挥作用。在此，我们表明蛋白精氨酸甲基转移酶1（PRMT1）与转录共激活因子p300/CREB结合蛋白、CARM1和聚（ADP-核糖）聚合酶1协同共激活巨噬细胞炎性蛋白2和人类免疫缺陷病毒1长末端重复启动子处的NF-κB依赖性基因表达。PRMT1在体内与聚（ADP-核糖）聚合酶1和NF-κB形成复合物，并在体外直接与NF-κB亚基p65相互作用。PRMT1的甲基转移酶活性对于其与CARM1和p300/CREB结合蛋白相关的共激活功能似乎至关重要。这些结果表明PRMT1和CARM1之间的协同作用是NF-κB依赖性基因表达所必需的。
