Variation in Genome-wide NF-kappaB RELA Binding Sites upon Microbial Stimuli and Identification of a Virus Response Profile

NF-kB transcription factors are master regulators of the innate immune response. Activated downstream of pathogen recognition receptors, they regulate the expression of genes to help fighting infections as well as recruiting the adaptive immune system. NF-kB responds to a wide variety of signals, but the processes by which stimulus-specificity is attained remain unclear. Here, we characterized the response of one NF-kB member, RELA, to four stimuli mimicking infection in human nasopharyngeal epithelial cells. Comparing genome-wide RELA binding, we observed stimulus-specific sites, although most sites overlapped across stimuli. Specifically, the response to Poly I:C - mimicking viral dsRNA and signalling through TLR3 - induced a distinct RELA profile, binding in the vicinity of antiviral genes and correlating with corresponding gene expression. This group of binding sites was also enriched in Interferon Regulatory Factor (IRF) motifs and showed overlapping with IRFs binding sites. A novel NF-kB target, OASL was further validated and showed TLR3-specific activation. This work showed that some RELA DNA binding sites varied in activation response following different stimulations and that interaction with more specialized factors could help achieve this stimulus-specific activity. Our data provide a genomic view of regulated host response to different pathogen stimuli.