Objectif Tissue responses to microbial and endogenous danger signals involve the activation of both resident and monocyte-derived macrophages, as well as the coordinated inducible expression of hundreds of inflammatory genes. Gene transcription is controlled by the information contained in thousands of genomic regulatory elements (enhancers and promoters), which is first read by transcription factors (TFs) and then integrated and relayed to the transcriptional machinery via an array of co-regulators with disparate biochemical activities and functions. The recent work of several groups, including our own, has extensively characterized how in macrophages the genomic regulatory sequences controlling inflammatory gene expression are coordinately bound and activated by myeloid lineage-determining TFs and broadly expressed stimulus-activated TFs. However, we still have a very incomplete understanding of the necessary next step in the process, namely how distinct combinations of DNA-bound TFs regulate recruitment and function of the co-regulators and machineries that control gene transcription. Here, I propose to systematically identify the complement of co-regulators that control the induction of inflammatory genes in macrophages, which will be then mechanistically and functionally characterized both in vitro and in vivo. By integrating cutting edge genomic and computational approaches with focused genetic screens and biochemical analyses, and eventually validating relevant results in mouse models, this project aims at obtaining an unprecedented level of understanding of the information flow linking genomic regulatory elements to inflammatory gene transcription. Champ scientifique natural sciencesbiological sciencesgenetics Mots‑clés Macrophages transcription transcription factors chromatin epigenetics and gene regulation Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-ADG-2015 - ERC Advanced Grant Appel à propositions ERC-2015-AdG Voir d’autres projets de cet appel Régime de financement ERC-ADG - Advanced Grant Institution d’accueil ISTITUTO EUROPEO DI ONCOLOGIA SRL Contribution nette de l'UE € 1 377 911,71 Adresse VIA FILODRAMMATICI 10 20121 Milano Italie Voir sur la carte Région Nord-Ovest Lombardia Milano Type d’activité Private for-profit entities (excluding Higher or Secondary Education Establishments) Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 377 911,71 Bénéficiaires (2) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire ISTITUTO EUROPEO DI ONCOLOGIA SRL Italie Contribution nette de l'UE € 1 377 911,71 Adresse VIA FILODRAMMATICI 10 20121 Milano Voir sur la carte Région Nord-Ovest Lombardia Milano Type d’activité Private for-profit entities (excluding Higher or Secondary Education Establishments) Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 377 911,71 HUMANITAS UNIVERSITY Participation terminée Italie Contribution nette de l'UE € 1 122 088,29 Adresse VIA RITA LEVI MONTALCINI SNC 20090 Pieve Emanuele Voir sur la carte Région Nord-Ovest Lombardia Milano Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 122 088,29
