Objective The majority of nuclear receptors (NRs) signal as heterodimers (HDs) with the promiscuous retinoid X receptors (RXRs). Heterodimerization introduces several key regulatory features to the RXR family,as it specifies response element recognition and allows dual ligand input in a HD-specific manner. Together these features allow the large family of RXR heterodimerizing NRs to establish a plethora of cognate ligand-dependent gene networks that regulate major aspects of cell and organ function during embryoge nesis and in the adult. Importantly, NRs are drugable and play central roles in major diseases like cancer, diabetes and atherosclerosis. HD target gene regulation has only been investigated by a gene-by-gene approach. Thus, key aspects of this regulator y network, e.g. identity of primary targets and their response dynamics, sharing of targets by different HDs, NR subtype and ligand dependency, are entirely unknown. The main objective of X-TRA-NET is to develop and employ chromatin-immunoprecipitation ( ChIP) microarray technology to explore the complex transcriptional network of RXR and its partners. X-TRA-NET will use these unique microarrays to investigate the impact of position and binding site diversity on the mechanisms of RXR target gene activati on. The complex interplay between cellular context, target site diversity and receptor subtype specificity will also be addressed. The microarrays will be used to investigate how treatment of cell culture and animal models with different ligands targeti ng the heterodimerization partner, or RXR itself, differentially affects recruitment of the NRs and their associated co-factors to target sites. Thus, X-TRA-NET aims to provide the first proof of concept for the use of ChIP-chip technology in NR ligand p rofiling. This would represent a major leap forward in NR pharmacogenomics by providing the missing link between in vitro ligand binding studies and testing these putative drugs in animals. Fields of science medical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosismedical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesclinical medicineoncology Programme(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Topic(s) LSH-2004-1.1.0-1 - Topics for Specific Targeted Research Project in the area of Fundamental knowledge and basic tools for functional genomics in all organisms Call for proposal FP6-2004-LIFESCIHEALTH-5 See other projects for this call Funding Scheme STREP - Specific Targeted Research Project Coordinator UNIVERSITY OF SOUTHERN DENMARK EU contribution No data Address Campusvej 55 ODENSE M Denmark See on map Links Website Opens in new window Total cost No data Participants (4) Sort alphabetically Sort by EU Contribution Expand all Collapse all CENTRE EUROPÉEN DE RECHERCHE EN BIOLOGIE ET MÉDECINE - GROUPEMENT D'INTÉRÊT ECONOMIQUE France EU contribution No data Address 1 rue Laurent Fries 10142 ILLKIRCH See on map Links Website Opens in new window Total cost No data GENFIT France EU contribution No data Address 885, Avenue Eugène Avinée LOOS See on map Links Website Opens in new window Total cost No data STICHTING KATHOLIEKE UNIVERSITEIT Netherlands EU contribution No data Address Toernooiveld 1 NIJMEGEN See on map Links Website Opens in new window Total cost No data UNIVERSITÉ DE LILLE 2 - DROIT ET SANTÉ France EU contribution No data Address Rue Paul Duez,42 LILLE See on map Links Website Opens in new window Total cost No data
