Chromatin is controlled by post-translational modification of its core subunits, the histones, and other transcriptional factors. The enzymes catalyzing these modifications include acetyltransferases, (HATs), deacetylases (HDACs), methyltransferases (MTs), kinases, and others. The enzymes work together to promote dynamic patterns of modification that help to specify epigenetic processes. We study several classes of the chromatin modifying enzymes to understand the range of their in vivo functions, including mechanisms of their activity, genomic targeting, and interaction with transcriptional and DNA repair complexes. Our experimental approaches include genetic, genomic and biochemical strategies to understand the MYST family HATs, the SIR2 family HDACs, and several classes of evolutionarily conserved MTs.