Project description DEENESFRITPL Dissecting the regulation of gene expression during development Multicellular organisms rely on a carefully regulated gene expression programme that drives cell differentiation and specification. The activity of developmental genes is tuned by cis-regulatory landscapes, but the precise mechanism remains elusive. The EU-funded CisTune project will focus on the X-inactive specific transcript (Xist) locus, which controls X-chromosome inactivation during development. The Xist seems to integrate sex- and developmental time-related signals to ensure transcription from only one chromosome in each cell. The project will unveil the regulatory principles that control the activity of the mammalian genome during development, offering important knowledge on the complexity of gene regulation. Show the project objective Hide the project objective Objective Development of multicellular organisms relies on differential gene activation in a single genome. In response to multiple quantitative signals, cell-type specific transcriptional programs are established that determine cell identify. Their perturbation can result in pathologies such as cancer. Large cis-regulatory landscapes integrate information on cell state, space and time to precisely tune the activity of developmental genes. How cis-regulatory landscapes decode multiple quantitative signals remains poorly understood. CisTune aims at gaining a functional and mechanistic understanding of how regulator levels are sensed, how the input from multiple regulators is integrated and how information is processed by cis-regulatory landscapes.CisTune will use the Xist locus as a model, which controls X-chromosome inactivation, an essential developmental process in mammals. Xist's cis-regulatory landscape integrates multiple quantitative input signals that transmit information on sex and developmental time, to ensure up-regulation from one X chromosome in each female cell. In CisTune we will thus study an essential process in great depth to identify regulatory principles that control activity of the mammalian genome during development.CisTune will use an interdisciplinary approach at the intersection of systems biology, epigenetics and gene regulation, where highly multiplexed perturbation experiments of endogenous genes are interpreted with the help of mathematical models. We will build on recent technological breakthroughs, including single-cell genomics and high-throughput CRISPR screens, which we will complement with a new approach to functionally link sequence elements to their input signals. CisTune has the potential to overcome challenges that have prevented mammalian quantitative biology of gene regulation to becoming more broadly applied and will set the stage for investigating gene regulation across multiple layers of complexity. Fields of science natural sciencesbiological scienceszoologymammalogynatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesgeneticsepigeneticsnatural sciencesmathematicsapplied mathematicsmathematical model Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2020-STG - ERC STARTING GRANTS Call for proposal ERC-2020-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Net EU contribution € 1 494 375,00 Address HOFGARTENSTRASSE 8 80539 Munchen Germany See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 494 375,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Germany Net EU contribution € 1 494 375,00 Address HOFGARTENSTRASSE 8 80539 Munchen See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 494 375,00
