IRF5:RelA interaction targets inflammatory genes in macrophages.

Journal article

Interferon Regulatory Factor 5 (IRF5) plays a major role in setting up an inflammatory macrophage phenotype, but the molecular basis of its transcriptional activity is not fully understood. In this study, we conduct a comprehensive genome-wide analysis of IRF5 recruitment in macrophages stimulated with bacterial lipopolysaccharide and discover that IRF5 binds to regulatory elements of highly transcribed genes. Analysis of protein:DNA microarrays demonstrates that IRF5 recognizes the canonical IRF-binding (interferon-stimulated response element [ISRE]) motif in vitro. However, IRF5 binding in vivo appears to rely on its interactions with other proteins. IRF5 binds to a noncanonical composite PU.1:ISRE motif, and its recruitment is aided by RelA. Global gene expression analysis in macrophages deficient in IRF5 and RelA highlights the direct role of the RelA:IRF5 cistrome in regulation of a subset of key inflammatory genes. We map the RelA:IRF5 interaction domain and suggest that interfering with it would offer selective targeting of macrophage inflammatory activities.

Authors: Saliba, D; Heger, A; Eames, H; Oikonomopoulos, S; Teixeira, A

• Publication status: Published
• Journal: Cell reports
• Volume: 8
• Issue: 5
• Pages: 1308-1317
• Publication date: 2014-09-01
• DOI: 10.1016/j.celrep.2014.07.034
• EISSN: 2211-1247
• ISSN: 2211-1247
• Language: English