The gypsy Insulator Can Act as a Promoter-Specific Transcriptional Stimulator

Abstract

Insulators define chromosomal domains such that an enhancer in one domain cannot activate a promoter in a different domain. We show that the Drosophila gypsy insulator behaves as acis-stimulatory element in the larval fat body. Transcriptional stimulation by the insulator is distance dependent, as expected for a promoter element as opposed to an enhancer. Stimulation of a test alcohol dehydrogenase promoter requires a binding site for a GATA transcription factor, suggesting that the insulator may be facilitating access of this DNA binding protein to the promoter. Short-range stimulation requires both the Suppressor of Hairy-wing protein and the Mod(mdg4)-62.7 protein encoded by the trithorax group gene mod(mdg4). In the absence of interaction with Mod(mdg4)-62.7, the insulator is converted into a short-range transcriptional repressor but retains some cis-stimulatory activity over longer distances. These results indicate that insulator and promoter sequences share important characteristics and are not entirely distinct. We propose that the gypsy insulator can function as a promoter element and may be analogous to promoter-proximal regulatory modules that integrate input from multiple distal enhancer sequences.

ACKNOWLEDGMENTS

We thank P. Geyer for providing Drosophila stocks. We also thank P. Geyer, V. Corces, and D. Dorsett for sharing with us their unpublished results.

W.W. was supported in part by a Merit Fellowship from the University of Louisville Center for Genetics and Molecular Medicine. This work was supported by the University of Louisville and by NIH monies to M.D.B.