Epromoters

A central dogma in the gene regulation field implies that gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. By combining an original high-throughput reporter assay and CRISPR genetic manipulations we recently demonstrated that a subset of gene promoters, termed Epromoters, works “also” as bona fide enhancers and regulate distal gene expression. Here, we hypothesise that Epromoters play a key role in the coordination of rapid gene induction in the stress response, in particular during inflammation. In this proposal we will study the functional role of Epromoters in the interferon and serum response, determine their impact in genome topology, and establish in vivo models to assess Epromoter variation in inflammatory diseases. Our systematic approach will unravel the basic molecular mechanisms of this novel type of regulatory elements and shed the basis of their potential involvement in diseases.