Elucidating the mechanisms of the human transcriptional regulatory network is a major challenge of the post-genomic era. One important aspect is the identification and functional analysis of non-coding DNA. Genomic sequence comparisons between related species can guide the discovery of cis-regulatory sequences. Using this technique, we identify a conserved region CNSmd of approx. 800 bp in size, 15 kb upstream of the renin gene. The renin gene plays a pivotal role for mammalian blood pressure regulation and electrolyte balance. To analyze the cis-regulatory role of this region in detail we perform 132 combinatorial reporter gene assays. To dissect the role of individual sub-regions we fit several mathematical models to the experimental data. We show that a nonlinear switch model fits best the experimental data and that one sub-region has a dominant effect on promoter activity. A mapping of the sub-sequences on conservation data reveals that the dominant regulatory region is the one with the highest multi-species conservation score.