Epigenetics research focuses on the study of heritable gene regulatory mechanisms that do not involve changes of the DNA sequence. Such mechanisms include post-translational modifications of histone proteins that organize the genome in the nucleus into a nucleoprotein complex called chromatin, and which are of key importance in development and disease. Chemical biology tools as developed by my group, in particular synthetic peptide and protein chemistry, have been critical to elucidate epigenetic signaling mechanisms. As outlined below, they allow the reconstitution of chromatin carrying defined modifications and thus the elucidation of detailed molecular mechanisms.