Objective Histone modifications play important roles in chromatin regulation. Methylation of lysine-residues on histone H3 and H4 affects processes ranging from transcriptional regulation to epigenetic silencing. The recent identification of histone lysine demethylases has clearly demonstrated that histone methylation is not a stable epigenetic mark, as previously assumed. The largest family of demethylases employ 2-oxoglutarate as a co-substrate. Each of these demethylases displays remarkable sequence and methylation-state specificity; however, little is known about the mechanisms by which this selectivity is achieved. For the JMJD2 subfamily of histone demethylases the selectivity for different peptide lengths, sequences and methylation states will be investigated using both biochemical and biophysical approaches. The detailed chemical mechanism of these demethylases will also be investigated using a variety of methods, including EPR, Mössbauer and UV-Visible spectroscopic methods, in combination with more conventional biochemical assays. The oxygen-dependence of these enzymes will also be investigated. Finally, peptide arrays of combinatorially-modified histone peptide fragments will provide insights into the ability of these demethylases to recognise and demethylate multiply-modified histone sequences. Overall, these studies will provide molecular detail on how chromatin is regulated by histone demethylases. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesnatural sciencesbiological sciencesgeneticsepigenetics Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2009-IEF - Marie Curie Action: "Intra-European Fellowships for Career Development" Call for proposal FP7-PEOPLE-2009-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD EU contribution € 173 240,80 Address WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford United Kingdom See on map Region South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Activity type Higher or Secondary Education Establishments Administrative Contact Linda Pialek (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data