Gene silencing is required to stably maintain distinct patterns of gene 
expression during eukaryotic development and has been correlated with the 
induction of chromatin domains that restrict gene activity. We describe the 
isolation of human (EZH2) and mouse (Ezh1) homologues of the Drosophila 
Polycomb-group (Pc-G) gene Enhancer of zeste [E(z)], a crucial regulator of 
homeotic gene expression implicated in the assembly of repressive protein 
complexes in chromatin. Mammalian homologues of E(z) are encoded by two distinct 
loci in mouse and man, and the two murine Ezh genes display complementary 
expression profiles during mouse development. The E(z) gene family reveals a 
striking functional conservation in mediating gene repression in eukaryotic 
chromatin: extra gene copies of human EZH2 or Drosophila E(z) in transgenic 
flies enhance position effect variegation of the heterochromatin-associated 
white gene, and expression of either human EZH2 or murine Ezh1 restores gene 
repression in Saccharomyces cerevisiae mutants that are impaired in telomeric 
silencing. Together, these data provide a functional link between Pc-G-dependent 
gene repression and inactive chromatin domains, and indicate that silencing 
mechanism(s) may be broadly conserved in eukaryotes.