Objective (Hydroxy)methylation of cytosine residues in eukaryotic DNA represents a major means to regulate gene expression during development. These modifications are considered to be epigenetic marks, since they have a profound impact on phenotype, but are inherited from mother to daughter cells independent of the underlying DNA sequence. Large efforts are currently underway to profile genome-wide DNA (hydroxy)methylation patterns in model organisms and in clinical studies, since aberrant DNA (hydroxy)methylation is a hallmark of cancer. Strikingly, the molecular mechanisms underlying the link between DNA (hydroxy)methylation and gene expression remain elusive. Although causal links are thought to arise from differential recruitment of transcription factors to (hydroxy)methylated DNA in a regulated manner during development, technical limitations have thus far prevented unbiased interaction screenings to investigate this hypothesis in detail. By using a unique combination of state-of-the-art quantitative mass spectrometry-based proteomics technology, genomics approaches and biochemical experiments, I will systematically investigate which proteins interact with or are repelled by (hydroxy)methylated DNA during stem cell differentiation into a neuronal lineage. Furthermore, I will investigate whether and to what extent these interactions regulate gene expression programs and lineage commitment. The results of these studies will reveal the mechanisms through which dynamic DNA (hydroxy)methylation patterns dictate cellular responses. This is anticipated to significantly increase our understanding of eukaryotic development and the role of epigenetics herein. Furthermore, these studies will pave the way for designing strategies aimed at interfering with altered epigenetics patterns in disease. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsepigenetics 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) Topic(s) ERC-SG-LS2 - ERC Starting Grant - Genetics,Genomics,Bioinformatics and Systems Biology Call for proposal ERC-2012-StG_20111109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution STICHTING RADBOUD UNIVERSITEIT EU contribution € 1 499 776,00 Address HOUTLAAN 4 6525 XZ Nijmegen Netherlands See on map Region Oost-Nederland Gelderland Arnhem/Nijmegen Activity type Higher or Secondary Education Establishments Principal investigator Michiel Vermeulen (Dr.) Administrative Contact Marion Bussemakers (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all STICHTING RADBOUD UNIVERSITEIT Netherlands EU contribution € 1 499 776,00 Address HOUTLAAN 4 6525 XZ Nijmegen See on map Region Oost-Nederland Gelderland Arnhem/Nijmegen Activity type Higher or Secondary Education Establishments Principal investigator Michiel Vermeulen (Dr.) Administrative Contact Marion Bussemakers (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data UNIVERSITAIR MEDISCH CENTRUM UTRECHT Participation ended Netherlands EU contribution No data Address HEIDELBERGLAAN 100 3584 CX Utrecht See on map Region West-Nederland Utrecht Utrecht Activity type Higher or Secondary Education Establishments Administrative Contact Joost Warsanis (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data