“Our research will help elucidate how deregulation of normal chromatin function leads to diseases such as cancer or neuronal disorders”
Most genetic information in eukaryotic cells is stored within the nucleus in the form of chromatin. Two key mechanisms that regulate the functional state of chromatin in mammals are DNA methylation and the post-translational modification of histone proteins, both of which convey epigenetic information. Chromatin regulatory factors called ‘epigenetic effector molecules’ recognise methylated DNA or modified histones through their different binding domains and subsequently orchestrate biological events.
Since chromatin is a large macromolecular assembly, modifications most likely act in a concerted manner. However, it is still unclear how the information contained in combinatorial modification patterns on DNA and histones is interpreted. Our group investigates how combinations of DNA and histone modifications regulate the activity of chromatin. Employing methods from chemical biology, biochemistry and proteomics, in conjunction with tissue culture and genomic technologies, we study proteins that recognise DNA and histone modification patterns in the context of chromatin.
We focus on identifying new factors that integrate information contained in multiple chromatin modifications on nucleosomes, and understanding how these factors operate at the molecular level. We are particularly interested in molecular mechanisms underlying epigenetic gene regulation events during DNA replication, tumour formation and differentiation.
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