Cel In multicellular organisms, during embryogenesis and tissue homeostasis the differentiation of pluripotent stem cells into a variety of specialized cell types is governed by diverse transcriptional programs, the establishment and maintenance of which rely on epigenetic mechanisms, such as chromatin modifications. Over the past years, a large number of post-translational modifications of histones as well as enzymes responsible for either positioning or removal of these marks were characterized. Genome-wide studies mapping the distribution of histone modifications revealed a complex epigenetic landscape on eukaryotic chromosomes. In particular, distinct chromatin signatures were recently associated with enhancer elements, cis-acting DNA sequences inducing transcription from target promoters. However, whether the deposition of specific marks at enhancers is a pre-requisite for their activity or a mere consequence of the recruitment of histone-modifying complexes at their target promoters is an entirely open question.The aim of this proposal is to define the biological significance of histone modifications covering enhancer sequences in vivo. To perform this study we will generate transgenic mice allowing us to target histone-modifying activities at enhancers using a recently introduced technology based on transcription activator–like effectors (TALEs). The developing limb will serve as a model system since several well-defined enhancers are active specifically in this structure. We will validate this approach by assessing changes in histone marks over enhancer sequences in transgenic versus wild type mice. Next, we will determine how such changes affect the transcriptional status of the endogenous target gene of the enhancer by scoring both RNA levels and limb phenotypes. The results of this study are likely to have a major impact on our understanding of chromatin functions in transcriptional regulation. Dziedzina nauki natural sciencesbiological sciencesdevelopmental biologymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesbasic medicinephysiologyhomeostasisnatural sciencesbiological sciencesgeneticsepigeneticsnatural sciencesbiological sciencesgeneticsgenomeseukaryotic genomes Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2012-CIG - Marie-Curie Action: "Career Integration Grants" Zaproszenie do składania wniosków FP7-PEOPLE-2012-CIG Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-CIG - Support for training and career development of researcher (CIG) Koordynator INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH Wkład UE € 75 000,00 Adres ACKERMANNWEG 4 55128 Mainz Niemcy Zobacz na mapie Region Rheinland-Pfalz Rheinhessen-Pfalz Mainz, Kreisfreie Stadt Rodzaj działalności Research Organisations Kontakt administracyjny Franziska Martin (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych