Transvection, a chromosome pairing-dependent form of trans-based gene regulation, is widespread in the Drosophila melanogaster genome. Recent studies demonstrate that transvection is sensitive to cell environment and type in D. melanogaster, implicating transvection as a complex trait. To test this possibility, we first established that trans-interactions previously documented at the Malic enzyme (Men) locus are transvection (i.e., pairing-dependent). We then characterized the sensitivity of transvection at the Men locus to changes in the environment (temperature) and genetic background (third chromosome). Transvection varied significantly across genetic backgrounds and was significantly reduced by changes in temperature, and the two factors interacted to further modify transvection, while cis-based gene regulation remained unchanged by temperature. To determine if differences in transvection observed across genetic background and temperature are related to their effects on transcription factor expression, and possibly the presence or absence of binding sites for these transcription factors within the Men locus, we tested the relationship between Men expression and five transcription factors with binding sites near the Men transcription start sit (TSS). We found correlations between the expression of at least one transcription factor, Abd-B, and the presence of binding sites for that factor, and Men expression across changes in the environment. We also determined that changes in Abd-B expression can directly affect Men expression in cis, suggesting that cis and trans-regulation can share regulatory components in at least some cases. Together, our findings stress the importance of studying genetic interactions from a dynamic perspective by incorporating both genetic and environmental variation.