Polycomb group proteins set the stage for early lineage commitment.

Precise control of gene expression patterns is critical for the specification of cellular diversity during metazoan development. Polycomb group (PcG) proteins comprise a class of transcriptional modifiers that have dynamic and essential roles in regulating a number of key processes including lineage commitment. How this is accomplished during mammalian development is incompletely understood. Here, we discuss recent studies in embryonic stem cells (ESCs) that provide critical new insights into how PcG proteins may be targeted to genomic sites as well as the mechanisms by which these regulators influence gene expression and multilineage differentiation in mammals.