The PTS element mediates heritable long range enhancer-promoter interactions in transgenic embryos. J. Zhou , Q. Lin , Q. Chen , D. Wu. Dept Molec Gen, The Wistar Inst, Philadelphia, PA.

   The Drosophila Bithorax gene complex (BX-C) employs large complex control regions to ensure precise regulation of the Homeotic selector genes. Recently, specialized cis-regulatory elements such as Fab-7 and Fab-8 have been identified from the Abdominal-B (Abd-B) locus of the BX-C. These elements function as domain boundaries to protect individual enhancer domains, but paradoxically, they also block enhancer-promoter interactions in transgenic flies. This suggests that Abd-B enhancers must be able to overcome the Fab insulators in the endogenous location. The recently identified Promoter Targeting Sequence (PTS) from the 3' regulatory region of Abd-B offers an insight of how this may be achieved: the PTS has an anti-insulator activity, it allows an enhancer to bypass an intervening insulator and activate a promoter. Here we report that the PTS facilitates enhancers that are located far away from the promoter. It also restricts the enhancer activity to only a single promoter when multiple promoters are present in the transgene. Interestingly, the PTS requires an insulator to initiate its function but the insulator can be deleted with no effect on enhancer-promoter interactions once promoter targeting is established. The most distinctive feature is that the PTS mediated activities are heritable in all successive generations. These activities suggest that the PTS functions as an epigenetic element to mediate heritable long-range enhancer-promoter communications in the BX-C.