Genome-wide Characterization And Computational Identification Of Cis-regulatory Modules

Transcriptional regulation plays an essential role in orchestrated temporal and spacial regulation of gene expression in various biological processes. The regulatory mechanisms for gene expression are integrated at three hierarchical levels. The first is the sequence level, i.e. the 1D organization of functional sequence elements in the genome. This level includes all coding regions, the wide variety of regulatory sequences that bind sequence-specific protein factors, and sequence elements that may have a role in determining the 3D folding of the chromatin fibre. The second is the chromatin level, which allows switching between different functional states. Switching between a state that suppresses transcription and one that is permissive for gene activity probably occurs at the level of the gene cluster, involving changes in chromatin structure that are controlled by the interplay between histone modification, DNA methylation, and a variety of repressive and activating mechanisms. This regulatory level is combined with control mechanisms that switch individual genes in the cluster on and off, depending on the properties of the promoter. The third level is the nuclear level, which includes the dynamic 3D spatial organization of the genome inside the cell nucleus. The nucleus is structurally and functionally compartmentalized and epigenetic regulation of gene expression may involve repositioning of loci in the nucleus through changes in large-scale chromatin structure.On the sequence level, the regulation via the interactions between trans-acting factors and cis-regulatory sequences is the primary and conserved mechanism for controlling differential gene expression. Transcription factors, a large group of trans-acting factors, can change the transcriptional activity by binding specific DNA sequence, transcription factor binding site (TFBS) in the cis-regulatory regions of target genes. TFBS is usually 5 to 20 bp in length and situated variously relative to the transcription initial site (TIS) of a given gene. A set of transcription factors bound on a cis-regulatory region usually cooperates as a functional unit, called cis-regulatory module (CRM), to regulate gene expression. Identification of CRM is a challenging but promising topic in functional genomics, especially in computational biology.Some computational methods for CRMs prediction were successfully established in yeast, sea urchin, Drosophila and Xenopus. However, such studies of higher eukaryotic genome remain challenging, mainly because of the much larger intergenic regions in...