Polycomb group proteins are critical to maintaining gene repression established 
during Drosophila development. Part of this group forms the PRC2 complex 
containing Ez that catalyzes di- and trimethylation of histone H3 lysine 27 
(H3K37me2/3), marks repressive to transcription. We report that the mammalian 
homologs Ezh1 and Ezh2 form similar PRC2 complexes but exhibit contrasting 
repressive roles. While PRC2-Ezh2 catalyzes H3K27me2/3 and its knockdown affects 
global H3K27me2/3 levels, PRC2-Ezh1 performs this function weakly. In 
accordance, Ezh1 knockdown was ineffectual on global H3K27me2/3 levels. Instead, 
PRC2-Ezh1 directly and robustly represses transcription from chromatinized 
templates and compacts chromatin in the absence of the methyltransferase 
cofactor SAM, as evidenced by electron microscopy. Ezh1 targets a subset of Ezh2 
genes, yet Ezh1 is more abundant in nonproliferative adult organs while Ezh2 
expression is tightly associated with proliferation, as evidenced when analyzing 
aging mouse kidney. These results might reflect subfunctionalization of a PcG 
protein during evolution.