Abstract
Among the most important histone methyltransferases for metazoan development are EZH1/2 and their homologs, which methylate histone H3 lysine 27 and act as part of a highly conserved set of chromatin regulators called Polycomb Group (PcG) proteins. Reaching a precise understanding of the roles of PcG proteins in the orchestration of differentiation and the maintenance of cell identity requires a variety of genetic and molecular approaches. Here, we present a full suite of methods for the study of PcG proteins in early murine development, including mutant strain generation, embryonic stem cell derivation, epigenomic profiling, and immunofluorescence and in situ hybridization.