Silencing refers to a particular type of transcriptional repression characterized by the formation of a genetically heritable, repressed transcriptional state. Examples of silencing include position-effect variegation, X-chromosome inactivation, and the repression of the silent mating-type gene loci in yeast. Recent discoveries suggest that silencing in yeast, like silencing in larger eukaryotes, results from a particular chromatin structure that defines a chromosomal domain. In addition, a chromosomal origin of DNA replication is required for silencing in yeast, suggesting that DNA replication plays a role in forming functional chromosomal domains.