An appreciable fraction of the transcriptome differs in level of expression among individuals. Transcription factor (TF) expression and DNA binding causes cell-specific activation and repression of downstream targets, and TF expression levels vary across individuals. However, it is not clear how the strength of DNA binding for individual TFs translates into regulatory control, or whether a different set of binding motifs is used for strongly regulated modules. Here we integrate two publicly available data sets in Drosophila melanogaster, as well as conduct novel analyses, to address these questions.