Non-coding (nc) RNA silencing of imprinted genes in extra-embryonic tissues provides a good model for understanding an underexamined aspect of gene regulation by macro or long ncRNAs, that is their action as long-range cis-silencers. Numerous long intergenic ncRNAs (lincRNAs) have been recently discovered that are thought to regulate gene expression, some of which have been associated with disease. The few shown to regulate protein-coding genes are suggested to act by targeting repressive or active chromatin marks. Correlative evidence also indicates that imprinted macro ncRNAs cause long-range cis-silencing in placenta by targeting repressive histone modifications to imprinted promoters. It is timely, however, to consider alternative explanations consistent with the published data, whereby transcription alone could cause gene silencing at a distance.
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