X-chromosome inactivation provides a model for discovering the still emerging functions of non-coding RNAs, which exhibit diverse roles in regulating the epigenome. Combining recent insights into X-chromosome non-coding RNAs with the advent of next-generation sequencing technologies promises many new discoveries in interrogating the functions of non-coding RNAs at the genomic level. Global RNA-protein interaction information can now be queried by utilizing RNA immunoprecipitation followed by high-throughput sequencing (RIP-Seq), which has recently uncovered the diversity of the non-coding Polycomb transcriptome. In this chapter, we discuss non-coding RNAs of the X-inactivation center that have provided unique insights into RNA molecules as molecular switches, guides and tethers to the epigenome, and key participants in diverse regulatory pathways, including RNA interference and Polycomb silencing
