Regulatory sequences are also generally assumed to operate through their interactions with sequence-specific transcription factors and other regulatory proteins, but this assumption has been made in ignorance, until recently, of the extent of developmentally regulated transcription of ncRNAs from the genome, including many regions spanning enhancers and promoters (see, e.g., [45], [83]–[86]). The possibility is therefore that the genomes of mammals and other complex organisms encode a large repertoire of regulatory RNAs [4]. Indeed, the case has been made that a much higher degree of regulatory sophistication, aided by the co-option of the considerable powers of RNA to transmit sequence-specific information, was a prerequisite for the evolution of developmentally complex organisms [87],[88], and that many of these RNAs may be involved in the regulation of developmental processes, including the epigenetic trajectories that underpin them, for which there is increasing evidence [12],[89].
