Established cellular mechanisms related to the transcription of natural antisense transcripts. Top panel: over-expression of an antisense transcript (in blue) causes the modification and concomitant silencing of the sense promoter. The exact mechanism of how the repressive chromatin marks are established is yet unknown. Middle panel: in RNA masking, the antisense transcript directly interacts with the sense transcript (in red) and occludes regulatory sequences. Bottom panel: in RNA interference, sense and antisense transcripts hybridize and the double-stranded RNA is further processed by the RNA interference-linked enzymatic machinery. This may lead to post-transcriptional or transcriptional gene silencing. endo-siRNA, endogenous small interfering RNA; miRNA, microRNA.