The X as Model for RNA's Niche in Epigenomic Regulation

The X-linked region now known as the "X-inactivation center" (Xic) was once dominated by protein-coding genes but, with the rise of Eutherian mammals some 150-200 million years ago, became infiltrated by genes that produce long noncoding RNA (ncRNA). Some of the noncoding genes have been shown to play crucial roles during X-chromosome inactivation (XCI), including the targeting of chromatin modifiers to the X. The rapid establishment of ncRNA hints at a possible preference for long transcripts in some aspects of epigenetic regulation. This article discusses the role of RNA in XCI and considers the advantages RNA offers in delivering allelic, cis-limited, and locus-specific control. Unlike proteins and small RNAs, long ncRNAs are tethered to the site of transcription and effectively tag the allele of origin. Furthermore, long ncRNAs are drawn from larger sequence space than proteins and can mark a unique region in a complex genome. Thus, like their small RNA cousins, long ncRNAs may emerge as versatile and powerful regulators of the epigenome.