Regulation of Distal-less (Dll) gene expression by the DCRE in Drosophila. Dll is expressed in the Drosophila embryonic thorax, but not the abdomen. (A) Dll expression is controlled by two elements: the DMEact (an activator) and the DCRE (a mixed repressor and activator). DMEact is sufficient to drive expression in both the abdomen and the thorax, whereas the DCRE inhibits abdominal expression and enhances DMEact driven thoracic expression [70]; (B) Sequence of the DCRE, with known binding sites labeled. Slp and En binding sites are necessary for repressive DCRE activity in the abdomen [46,70]; (C) In the thorax, the chromatin structure of the Dll locus places the DMEact in proximity to the Dll promoter, whereas DNA looping between the DMEact regulatory region and the Dll promoter is not observed in abdominal segments [143]. These findings are consistent with results demonstrating that the DCRE “boosts” thoracic DMEact activation of Dll transcription via a mechanism dependent on Antp (the thoracic Hox factor) [70]. In contrast, the DCRE represses Dll transcription via mechanisms dependent on the abdominal Hox factors (Abd-A, Ubx and Abd-B) in the abdomen [46,70,138,139]. However, it is currently unclear if the thoracic and/or abdominal Hox factors directly regulate DNA looping between the distal leg enhancer and the proximal Dll promoter region.