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10.1016/j.celrep.2014.07.034

http://scihub22266oqcxt.onion/10.1016/j.celrep.2014.07.034
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suck abstract from ncbi


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pmid25159141
      Cell+Rep 2014 ; 8 (5 ): 1308-17
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  • IRF5:RelA interaction targets inflammatory genes in macrophages #MMPMID25159141
  • Saliba DG ; Heger A ; Eames HL ; Oikonomopoulos S ; Teixeira A ; Blazek K ; Androulidaki A ; Wong D ; Goh FG ; Weiss M ; Byrne A ; Pasparakis M ; Ragoussis J ; Udalova IA
  • Cell Rep 2014[Sep]; 8 (5 ): 1308-17 PMID25159141 show ga
  • 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.
  • |Animals [MESH]
  • |Cells, Cultured [MESH]
  • |Genome [MESH]
  • |Interferon Regulatory Factors/genetics/*metabolism [MESH]
  • |Macrophage Activation/genetics [MESH]
  • |Macrophages/immunology/*metabolism [MESH]
  • |Mice [MESH]
  • |Mice, Inbred C57BL [MESH]
  • |Protein Binding [MESH]
  • |Response Elements [MESH]
  • |Transcription Factor RelA/genetics/*metabolism [MESH]


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