In support of this proposition, there is now rapidly emerging evidence that many ncRNAs derived from either same or opposite strands act locally to regulate the epigenetic status and expression of nearby protein-coding genes, often involving the recruitment of chromatin-activator or repressor complexes [7], [13]–[16], [89], [154]–[157], with sense-antisense pairs in some cases being the substrate for the generation of siRNAs [63]–[65],[68]. Moreover the many deletion studies of gene promoter regions to define regulatory sequences have almost always assumed, physically and mechanistically, that resultant changes to expression patterns are due to the loss of cis-acting protein binding sites rather than deletions in the same or opposite strand ncRNAs that frequently traverse and are expressed from the same region. The complexity of these relationships is illustrated by the examples of the ncRNA DLeu2 (deleted in lymphocytic leukemia 2), which has multiple splice variants and lies antisense to genes in a region deleted in various malignancies [158], and the ncRNA ANRIL referred to earlier. Thus the interpretation of the mechanisms by which such mutations operate remains not only an open question but
