An important concern in the attempt of understanding the functional code of eukaryotic genes is to elucidate the control structures for regulating gene activation and suppression. One objective in the attempt to understand mechanisms of gene regulation is the elucidation of the regulatory network structure. A preliminary step of a detailed network analysis is identifying the transcription factor binding sites of a regulatory network. Known as cis-regulatory module (CRM), it is understood as part of the genome that comprises a set of short length binding sites. Gene regulatory systems are known to be quite stable during evolution, as compared to relatively frequent replication processes of genes and mutations of the coding sequences. This conservation property of regulatory code can advantageously be used for identifying cis-regulatory modules of potentially co-regulated genes. As the degree of similarity is expected to depend on the phylogenetic distance of homologs or orthologs, we favor an approach that is based on a comparison paradigm. The paper introduces a novel concept for measuring the similarity of cis-regulatory modules which can then be used in an algorithm for comparing regulatory regions. The proposed algorithm searches for pairs of similar modules, and a prototype implementation is applied to human and mouse liver sequences. The results are compared to that of random sequences, and it is shown that a clear decision about co-regulation is possible at this level.
['Klaus Ecker', 'Lonnie R. Welch']
A concept for ab initio prediction of cis-regulatory modules.