Dr. Salvatore Spicuglia - Dissection of cis-regulatory elements in normal and pa

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Dr. Salvatore Spicuglia - Dissection of cis-regulatory elements in normal and pathological conditions Salvatore Spicuglia Theories and Approaches of Genomic Complexity (TAGC), INSERM, Aix-Marseille University Dissection of cis-regulatory elements in normal and pathological conditions In our team, we have developed original approaches to understanding gene regulation in normal and pathological conditions. On the one hand, we pioneering the development of high-throughput reporter assays to study cis-regulatory function in mammals. We demonstrated the value of this approach to provide accurate quantification of enhancer and silencer activities and to lead to the discovery of new types of regulatory mechanisms. In particular, we discovered a subset of gene-promoters, termed Epromoters, that also work as bona fide enhancers and regulate distal gene expression. These Epromoters play an essential role during the inflammatory and stress response, and appear to be associated with pleiotropic genetic variants. On the other hand, we have generated a comprehensive resource of transcriptomic and epigenomic data covering human T cell precursors and a large set of T-acute lymphoblastic leukemia (T-ALL). This served as a frame to address several aspects of epigenetics deregulation in T-ALL and provided novel mechanistic cues of oncogenic development. Selected publications Hussain S, Sadouni N, van Essen D, Dao LTM, Ferré Q, Charbonnier G, Torres M, Gallardo F, Lecellier CH, Sexton T, Saccani S, Spicuglia S (2023). Short tandem repeats are important contributors to silencer elements in T cells. Nucleic Acids Res . Mar 17:gkad187 Belhocine M, Simonin M, Abad Flores JD, Cieslak A, Manosalva I, Pradel L, Smith C, Mathieu EL, Charbonnier G, Martens JHA, Stunnenberg HG, Maqbool MA, Mikulasova A, Russell LJ, Rico D, Puthier D, Ferrier P, Asnafi V*, Spicuglia S.* (2022). Dynamic of broad H3K4me3 domains uncover an epigenetic switch between cell identity and cancer-related genes. Genome Res . 32(7):1328-1342 Santiago-Algarra D, Souaid C, Singh H, Dao LTM, Hussain S, Medina-Rivera A, Ramirez-Navarro L, Castro-Mondragon JA, Sadouni N, Charbonnier G, Spicuglia S. (2021) Epromoters function as a hub to recruit key transcription factors required for the inflammatory response. Nat Commun . 12(1):6660 Cieslak, A., G. Charbonnier, M. Tesio, E. L. Mathieu, M. Belhocine, A. Touzart, C. Smith, G. Hypolite, G. P. Andrieu, J. H. A. Martens, E. Janssen-Megens, M. Gut, I. Gut, N. Boissel, A. Petit, D. Puthier, E. Macintyre, H. G. Stunnenberg, S. Spicuglia* and V. Asnafi* (2020). Blueprint of human thymopoiesis reveals molecular mechanisms of stage-specific TCR enhancer activation. J Exp Med 217(9): (9): e20192360 Dao LTM, Galindo-Albarrán AO, Castro-Mondragon JA, Andrieu-Soler C, Medina-Rivera A, Souaid C, Charbonnier G, Griffon A, Vanhille L, Stephen T, Alomairi J, Martin D, Torres M, Fernandez N, Soler E, van Helden J, Puthier D, Spicuglia S (2017). Genome-wide characterization of mammalian promoters with distal enhancer functions. Nat Genet . 49(7):1073-1081 Vanhille L., A. Griffon, M.A. Maqbool, J. Zacarias, L.T.M. Dao, N. Fernandez, B. Ballester, J.C. Andrau, S. Spicuglia (2015). CapStarr-seq: a high-throughput method for quantitative assessment of enhancer activity in mammals. Nat. Commun . 6:6905 Pekowska A, Benoukraf T, Zacarias-Cabeza J, Belhocine M, Koch F, Holota H, Imbert J, Andrau J.C, Ferrier P and Spicuglia S (2011). H3K4 tri-methylation provides an epigenetic signature of active enhancers. EMBO J . 30, 4198–10