Distance conservation of transcription regulatory motifs in human promoters

To understanding the interaction network among transcription-regulation elements in human is an immediate challenge for modern molecular biology. Here a central problem is how to extract evolutionary information and search the evolutionary conservation from the comparison of promoters of closely related species. Through the comparative studies of k-mer distribution in human and mouse transcription factor binding site (TFBS) sequences we have discovered that the average distance between a pair of transcription regulatory 7-mer motifs is conservative in human–mouse promoters. The distance conservation is a new kind of evolutionary conservation, not based on the strict location of bases in genome sequence. By utilizing the conservation of k-mer distance it will be helpful to propose a non-alignment-based approach for fast genome-wide discovery of transcription regulatory motifs. We demonstrated the distance conservation by genome-wide searching of conservative regulatory 7-mer motifs with successful rate 90%. Then, after defining human–mouse pair-distance divergence parameter we studied the tissue-specific motif pairs and found that the parameter for motif pairs is 11–16 times smaller than for their controls for 28 tissues and these pairs can be clearly differentiated on two-dimensional parameter plane. Finally, the mechanism of distance conservation was discussed briefly which is supposed to be related to the module structure of TFBSs.