The Combinatorics Of Cis-Regulatory Elements: From Cooperatively Acting Motifs To Gene Regulatory Networks

The specific binding of a transcription factor to its DNA target site – the cis-element – located in the gene promoter, is considered the pivotal event in gene transcriptional regulation. However, frequently, transcriptional regulation is not mediated by single binding events but by the cooperative binding of several transcription factors such that individual cis-elements function jointly as composite elements. Furthermore, promoter regions generally do not harbor only one, but several and different cis-elements resulting in complex interactions and divers expression patterns. Here, we review primarily bioinformatic approaches to capture this regulatory complexity and look at different algorithmic strategies and associated available software solutions to identify composite cis-elements. Furthermore, efforts to describe the resulting complexity of gene regulation and the relation to whole genome architectural properties are discussed. Finally, approaches and available web-based information resources to utilize information on transcription factor – target gene binding events to infer complex gene regulatory networks are presented.

Keywords: combinatorics, gene regulatory networks, regulatory modules, co-operative motifs, motif mining, co-occurance, network analysis.