All eukaryotes organize their genomes in the form of chromatin, a complex of DNA and dedicated packing proteins, so-called histones. In addition to compacting DNA, chromatin regulates the activity of encoded genes through posttranslational modifications of the histone proteins. Deciphering the complex crosstalk between histone modifications and gene activity represents a central challenge for biomedical science. Our group is developing and using chemical tools to study the physiological function of posttranslational histone modifications. To this end we combine methods from chemistry, biochemistry and molecular biology to probe a wide range of chromatin factors including chromatin binding proteins and histone-modifying enzymes.