CANCELLED - Genome-wide discovery of promoters with enhancer function
Salvatore Spicuglia completed a PhD in Immunology under the direction of Dr. Pierre Ferrier (1998-2002) at the Marseille Luminy Immunology Center (CIML, Marseille) where he studied the assembly and regulation of T cell receptors genes. He then joined the laboratory of Prof. Henk Stunnenberg at the Nijmegen Center of Medical Life Science (NCMLS, The Netherlands) where he works on the basic mechanisms of transcription (2003-2005). In 2005, he was recruited by the INSERM at the CIML and started developing large-scale analytical approaches to better understand epigenetic and transcriptional regulation during T cell differentiation. In 2011, he established an independent research group at the Technological Advances for Genomics and Clinic Laboratory (TAGC, Marseille). The work of his team is devoted to the characterization of epigenomes during differentiation of mouse and human T cells and the understanding of how epigenetics deregulation leads to oncogenic transformation. The team has recently developed a high-throughput reporter assay to assess enhancer activity. Using this approach, they discovered a new type of regulatory elements playing a dual role as transcriptional promoter and enhancer, a finding having important implications for the understanding of complex gene regulation in normal development and disease. Salvatore Spicuglia has been PI in over 13 French research projects, 2 European projects, and 2 international consortia. He was partner in the European large-scale research project Blueprint focusing on understanding the epigenomes of human blood cells.
2018 Prize "Coup d'Élan pour la recherche française" Bettencourt Schueller Foundation
2017 Inserm award for research excellence
2017 Roche and Mexican Health Society "basic science award" (regarding Galindo et al. Cell report 2016).
2003 University of Aix-Marseille II. Best PhD thesis award.
Thursday 26 March 2020 (12h15 - 13h00) - Génopode - Auditoire A
Gene expression in mammals is precisely regulated by combination of promoters and gene-distal regulatory regions, known as enhancers. Recent studies have shown broad similarities between enhancers and promoters and suggested that some promoters might also play enhancer functions. However, the extent of this type of promoters and whether they actually function to regulate the expression of distal genes have remained elusive. Here, by exploiting CapStarr-seq, a high-throughput enhancer reporter assay, we unravel a substantial proportion of mammalian promoters displaying enhancer activity, named hereafter Epromoters. Compared to classical promoters and distal enhancers, Epromoters display distinct genomic and epigenomic features and are associated with stress response. By using comprehensive CRISPR/Cas9 genomic deletions we demonstrated that Epromoters are frequently involved in cis-regulation of distal gene expression in their endogenous context, therefore functioning as bona fide enhancers. Furthermore, our results suggest that Epromoters might play an essential role in the coordination of rapid gene induction during the inflammatory response, and more generally upon cellular response to intra- and extra-cellular signals. These finding have important implications for the understanding of complex gene regulation in normal development and disease.