Transcription is the processes through which RNA is created from DNA. RNA is then used to make proteins, which do much of the work in the cell. The process through which transcription is activated varies across genes, cell types, individuals, and species, and it is not well understood. High-throughput sequencing has enabled us to evaluate aspects of this process in multiple contexts. We present computational methods to leverage large high-throughput sequencing data sets to identify associations between genetic variation and differences in transcriptional regulatory mechanisms. Our results provide insights into how different parts of transcriptional regulatory mechanisms work together.