Models of MIE enhancer action in bidirectional gene pair transcription. (A) Synchronizer model. This model proposes that the enhancer region activates its flanking genes bidirectionally and simultaneously (the on-on state). As a consequence, transcriptions of ie1/3 and ie2 are expected to be correlated on the single genome level. (B) Switch model. This model proposes that the enhancer region activates its flanking genes bidirectionally but alternately (on-off and off-on states). As a consequence, transcriptions of ie1/3 and ie2 are expected to be anticorrelated on the single genome level, whereas alternate activation leads to correlated transcriptions on a multiple genome level. Bidirectional head-to-head architecture and exon-intron structure of the mCMV MIE locus (24, 35, 36) are illustrated. Open reading frames are designated according to the nomenclature proposed by Rawlinson et al. (37). Yellow and blue cylinders symbolize exons of ie1/3 and ie2, respectively. Yellow- and blue-colored arrows indicate the 5′-3′ direction of transcription on the respective DNA strand. P, promoter; TF, transcription factor(s); TFBS, transcription factor binding site(s).