DISSECTION OF THE COORDINATED INTERFERON RESPONSE BY PROMOTER ELEMENTS WITH ENHANCER ACTIVITY
authors
keywords
- Epromoter
- Interferon alpha
- High throughput reporter assay
- Inflammatory response
- Gene regulation
document type
THESEabstract
Gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Previous results have demonstrated that a subset of gene promoters also termed Epromoters, works as bona fide enhancers and regulates distal gene expression. We hypothesized that Epromoters might play a key role in the coordination of rapid gene induction in the stress response, in particular during inflammation. Using a high-throughput reporter assay we explored the function of Epromoter in response to type I interferon. We found that STAT1/2 and IRF transcription factors preferentially bind to IFNa-induced Epromoters and distally regulate the activation of interferon-response genes. Similar observations were made in other types of inflammatory response. Our findings suggest that Epromoters might function as a hub to recruit key TFs required for coordinated regulation of gene clusters during the inflammatory response, and more generally upon cellular response to intraand extra-cellular signals.
