Objectif Sumoylation of proteins has emerged as a central regulatory mechanism influencing a wide range of cellular processes and is notably a key pathway facilitating cellular response to stress. Gene expression appears to be particularly regulated by sumoylation as many known SUMO substrates are transcription factors and cofactors. Moreover, key chromatin proteins, including the core histones, figure among the SUMO targets. The emerging paradigm for the proposed work is that sumoylation controls multiple aspects of chromatin structure and that sumoylated proteins are principal and instructive components of a dynamic chromatin scaffold that can respond to external cues. According to this view, sumoylation is expected to impact both global and specific transcriptional programs thereby affecting constitutive and inducible gene expression.The goal of this project is to define the role of sumoylation-mediated gene control in stress response and to analyze the impact of dysregulation of this pathway in inflammation and cancer with a primary focus on the intestinal tract. Our specific aims are to 1) Identify stress-regulated molecular players of the SUMO pathway, 2) Define the genome-wide organization of the SUMO chromatin landscape and its plasticity upon stress, 3) Probe the role of sumoylation in normal and pathological inflammatory response with an emphasis on acute and chronic colitis, 4) Explore the possible implication of the SUMO pathway in colon cancer.This project is supported by a wealth of preliminary data based on genomic approaches and mouse models for partial or complete loss of sumoylation. We expect our study to bring innovative concepts on sumoylation’s role in normal and disease states. Novel regulators of sumoylation will be identified, unsuspected transcriptional networks will be uncovered, determinants of human malignancies and inflammatory diseases will potentially be identified, with a view toward therapeutic strategies seeking to manipulate sumoylation. Champ scientifique medical and health scienceshealth sciencesinflammatory diseasesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologycolorectal cancer Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Appel à propositions ERC-2011-ADG_20110310 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil INSTITUT PASTEUR Contribution de l’UE € 2 499 996,00 Adresse RUE DU DOCTEUR ROUX 25-28 75724 Paris France Voir sur la carte Région Ile-de-France Ile-de-France Paris Type d’activité Research Organisations Contact administratif Sophie Ablott (Ms.) Chercheur principal Anne Dejean (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire INSTITUT PASTEUR France Contribution de l’UE € 2 499 996,00 Adresse RUE DU DOCTEUR ROUX 25-28 75724 Paris Voir sur la carte Région Ile-de-France Ile-de-France Paris Type d’activité Research Organisations Contact administratif Sophie Ablott (Ms.) Chercheur principal Anne Dejean (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée