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.
