Noncoding RNA localisation mechanisms in chromatin regulation

A number of noncoding RNAs (ncRNAs) have been demonstrated to play a role in transcriptional or chromatin regulation through their interaction with chromatin-modifying enzymes and transcription factors. Some of these RNAs can be visualised to be associated with specific loci, most strikingly the coating of the inactive X chromosome (Xi) by X inactive-specific transcript (Xist) RNA. Modulation of a number of ncRNAs leads to changes in the targeting of regulatory complexes to specific genomic sites. Mechanisms must therefore be in operation that direct ncRNA-protein complexes to specific sites in the genome.Dosage compensation in female mammals is achieved by silencing one copy of the two X chromosomes, termed 'X-chromosome inactivation' (XCI). The long ncRNA Xist is the key factor in initiating this process [1]. Xist is transcribed from the X-inactivation centre (Xic) of the future Xi and progressively coats the chromosome. This is accompanied by the appearance of repressive chromatin modifications, including those catalysed by polycomb repressive complex 2 (PRC2). Xist RNA has been proposed to play a direct role in the recruitment of PRC2 through protein-RNA interaction [2]. An unresolved question has been how the Xist-PRC2 complex becomes exclusively localised to the future Xi. Jeon and Lee addressed this problem by studying Xist expression from an inducible transgene in post-XCI embryonic fibroblasts and using in situ hybridization and RT-PCR to distinguish between endogenous and transgenic Xist expression [3]. Transgenic Xist RNA localised to the transgene, but, surprisingly, endogenous Xist RNA, normally localised only to Xi, was also seen to migrate to the transgene locus. Seeking to identify a DNA element necessary for this accumulation of Xist RNA, the authors identified a cluster of three Yin Yang 1 (YY1) binding sites within the Xist transgene, and, consistent with this, found that knockdown of YY1 expression also abrogated Xist localisation. Reasoning that