The Nuclear Factor-κB Engages CBP/p300 and Histone Acetyltransferase Activity for Transcriptional Activation of the Interleukin-6 Gene Promoter

• DOI: 10.1074/jbc.274.45.32091
• Publication Date: 2002-07-26T15:11:04Z
• Authors: Wim Vanden Berghe; Karolien De Bosscher; Elke Boone; Stéphane Plaisance; Guy Haegeman
• Keywords: Histone acetyltransferase; Acetyltransferases

Expression of the pleiotropic cytokine interleukin (IL)-6 can be stimulated by proinflammatory tumor necrosis factor (TNF) and microbial alkaloid staurosporine (STS). In this report, transcriptional mechanisms were thoroughly investigated. Whereas transcription factors binding to activator protein-1-, cAMP-responsive element-, CAAT enhancer-binding protein-responsive sequences are necessary for gene activation STS, nuclear (NF)-kappaB alone is responsible sufficient inducibility TNF, which reveals distinct signaling pathways both compounds. At cofactor level, element-binding protein-binding protein (CBP) or p300 potentiate basal induced IL-6 promoter via multiple protein-protein interactions with all bound DNA. However, strongest relies on p65 NF-kappaB subunit, specifically engages CBP/p300 maximal stimulation its histone acetyltransferase activity. Moreover, treatment chromatin-integrated constructions deacetylase inhibitor trichostatin A exclusively potentiates TNF-dependent (i.e. NF-kappaB-mediated) activation, while STS-stimulated activity remains completely unchanged. Similar observations recorded other natural NF-kappaB-driven promoters, namely IL-8 endothelial leukocyte adhesion molecule (ELAM). We conclude that, within an "enhanceosome-like" structure, central mediator TNF-induced expression, involving requiring