Recent transcriptome analyses show that substantial proportions of eukaryotic genomes can be copied into RNAs, many of which do not encode protein sequences. However, cells have developed mechanisms to control and counteract the high transcriptional activity of RNA polymerases in order to achieve cell-specific gene activity or to prevent the expression of deleterious sequences. Here we compare how two silencing modes - the Polycomb system and heterochromatin - are targeted, established and maintained at different chromosomal locations and how DNA-binding proteins and non-coding RNAs connect these epigenetically stable and heritable structures to the sequence information of the DNA.