Most of the genetic information in eukaryotic cells is stored within the nucleus in the form of chromatin. Two key mechanisms known to regulate the functional state of chromatin in mammals are the methylation of DNA and the post-translational modification of histone proteins. Due to the large number of possible modifications, epigenetic information can be stored in chromatin modification patterns. Chromatin modifications have been shown to regulate all DNA-associated processes, such as transcription, replication, and DNA repair, and play an important role in cell proliferation and differentiation. These functions are intimately linked to the faithful interpretation and inheritance of genetic information and the memory of a cell’s identity. Deregulation of these modifications and their modifying enzymes are implicated in many types of diseases, including cancer and neurological disorders. Many chromatin-regulating factors have been identified that recognise methylated DNA or modified histones. Such effector molecules use a range of different binding domains in order to establish and 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 the DNA and histones is interpreted. Our aim is to understand how combinations of DNA and histone modifications regulate the activity of chromatin. We employ the tools of chemical biology, biochemistry and proteomics in conjunction with tissue culture and genomic technologies in order to study proteins that can recognise DNA and histone modification patterns in the context of chromatin. We have developed a technique called SILAC nucleosome affinity purification that allows us to identify proteins that bind DNA or histone modifications on in vitro assembled nucleosomes using high-resolution mass spectrometry. We will use this technique for identifying new factors that integrate information contained in multiple chromatin modifications on nucleosomes and chromatin, and for understanding how they operate at the molecular level. We are particularly interested in the molecular mechanisms that underlie epigenetic gene regulation events during DNA replication, tumour formation and differentiation processes. Our research will help elucidate how chromatin modifications regulate cellular processes and how deregulation of normal chromatin function leads to diseases. Our ultimate goal is to identify the critical factors and to understand their molecular and cellular functions in order to develop drugs for epigenetic therapies against diseases such as cancer.