RNA has traditionally been viewed as the genomic “messenger” molecule, carrying the coding information from DNA to make proteins. However, an abundance of short and long noncoding RNAs also exist, many of which are likely to have regulatory roles. Little is known about the mechanisms of action of long noncoding RNAs, but many appear to act as “guides” that recruit protein regulatory complexes to specific genomic loci to control gene expression . Where these long noncoding RNAs contact the genome, and how they locate these regulatory targets, have been open questions. On page 1237973 of this issue, Engreitz et al. show that the mouse long noncoding RNA called X-inactive specific transcript (Xist) is initially targeted to specific loci across the X chromosome using a targeting mechanism that exploits three-dimensional chromosome topology.