Non-coding transcription at cis-regulatory elements: computational and experimental approaches

Mammalian genomes are pervasively transcribed, generating mostly RNAs with no coding potential that display different size, structure and interspecies sequence conservation. A prominent contribution to the ncRNA pool comes from the transcription of cis-regulatory elements, namely promoters, enhancers and locus control regions. While this phenomenon has been extensively documented, possible roles of such ncRNAs in gene regulation are still unclear. Addressing this issue will require experimental strategies dealing with the low abundance of enhancer-templated ncRNAs and aimed at specifically dissecting the relative role of transcription per se vs. RNA products. In this review, we first focus on the identification and characterization of cis-regulatory elements, highlighting the differences between emerging classes of ncRNAs associated to specific chromatin signatures. We then discuss current experimental strategies to dissect the function of nc transcription and computational approaches to the analysis and classification of regulatory sequences identified in next-generation sequencing experiments.