Epigenetics of imprinted long non-coding RNAs

Abstract

It is becoming increasingly evident that noncoding RNA (ncRNA) constitutes an important component of chromatin and that ncRNA has a critical role in organizing the chromatin architecture and epigenetic memory by acting as an interface with the chromatin modifying machinery. Xist is the only RNA that has been shown to regulate gene expression by modulating chromatin structure using a multilayered silencing pathway. Recent emerging evidence indicates that long ncRNAs such as Kcnq1ot1 and Air which map to the Kcnq1 and Igf2r imprinted gene clusters, respectively, mediate the transcriptional silencing of multiple genes by interacting with chromatin and recruiting the chromatin modifying machinery. Though there are some parallels in the mechanistic actions of Kcnq1ot1 and Air, they seem to differ greatly in the way they achieve the silencing of overlapping and nonoverlapping genes. By reviewing the latest available evidence, we propose that Kcnq1ot1 RNA itself seems to play a critical role in the bidirectional silencing of genes in the Kcnq1 domain, thus resembling the Xist RNA; whereas in the case of Air, the act of transcription plays a critical role in the silencing of the overlapping gene, whilst Air RNA itself mediates the silencing of nonoverlapping genes in a fashion similar to Kcnq1ot1 and Xist RNAs.