An evolutionary approach for identifying potential transcription factor binding sites: the renin gene as an example

Evolutionary pressure has resulted in the conservation of certain nucleotide sequences. These conserved regions are potentially important for certain functions. Here we give an example of a comparison between noncoding sequences combined with other independent database information to shed light onto the regulation of the renin gene, a gene that has great importance for cardiovascular and renal homeostasis. To combine the information regarding conservation and weight matrices of transcription factor (TF) binding sites, an algorithm was developed (TFprofile). Notably, a local peak in the resulting binding profile coincides with a previously experimentally identified regulatory region for the renin gene. The existence of further peaks in the binding profile in the conserved 3.9-kb-long hRENc DNA block upstream of the renin gene suggests additional regions of potential importance for gene regulation. The algorithm TFprofile may be used to integrate information on cross-species evolutionary conservation and aspects of TF binding characteristics to provide putative regulatory DNA regions for experimental verification.