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.
Lu
Jun
J
Laboratory of Theoretical Biophysics, Faculty of Science and Technology, Inner Mongolia University, Hohhot, China.
Luo
Liaofu
L
Zhang
Ying
Y
D000818:Animals; D017124:Conserved Sequence; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic / Q000235:genetics*