Promoter architecture of Drosophila genes regulated by Myocyte enhancer factor-2.

Abstract

To gain understanding into the mechanisms of transcriptional activation of muscle genes, we sought to determine if genes targeted by the myogenic transcription factor Myocyte enhancer factor-2 (MEF2) were enriched for specific core promoter elements. We identified 330 known MEF2 target promoters in Drosophila, and analyzed them for for the presence and location of 17 known consensus promoter sequences. As a control, we also searched all Drosophila RNA polymerase II-dependent promoters for the same sequences. We found that promoter motifs were readily detected in the MEF2 target dataset, and that many of them were slightly enriched in frequency compared to the control dataset. A prominent sequence over-represented in the MEF2 target genes was NDM2, that appeared in over 50% of MEF2 target genes and was 2.5-fold over-represented in MEF2 targets compared to background. To test the functional significance of NDM2, we identified two promoters containing a single copy of NDM2 plus an upstream MEF2 site, and tested the activity of these promoters in vivo. Both the sticks and stones and Kahuli fragments showed strong skeletal myoblast-specific expression of a lacZ reporter in embryos. However, the timing and level of reporter expression was unaffected when the NDM2 site in either element was mutated. These studies identify variations in promoter architecture for a set of regulated genes compared to all RNA polymerase II-dependent genes, and underline the potential redundancy in the activities of some core promoter elements.