Title
Mapping association between long-range cis-regulatory regions and their target genes using synteny.
Abstract
In chordates, long-range cis-regulatory regions are involved in the control of transcription initiation (either as repressors or enhancers). Their main characteristics are that (i) they can be located as far as 1 Mb away from the transcription start site of the target gene, (ii) they can regulate more than one gene, and (iii) they are usually orientation-independent. Therefore, proper characterization of functional interactions between long-range cis-regulatory regions and their target genes remains problematic. We present a novel method to predict such interactions based on the analysis of rearrangements between the human and 16 other vertebrate genomes. Our method is based on the assumption that genome rearrangements that would disrupt the functional interaction between a cis-regulatory region and its target gene are likely to be deleterious. Therefore, conservation of synteny through evolution would be an indication of a functional interaction. We use our algorithm to predict the association between a set of 123,905 human candidate regulatory regions to their target gene(s). This genome-wide map of interactions has many potential applications, including the selection of candidate regions prior to in vivo experimental characterization, a better characterization of regulatory regions involved in position effect diseases, and an improved understanding of the mechanisms and importance of long-range regulation. Supplementary Material is available online at www.liebertonline.com/cmb.
Year
DOI
Venue
2011
10.1089/cmb.2011.0088
JOURNAL OF COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
evolution,genomic rearrangements,genomics,multiple alignment,phylogenetic analyses,regulatory regions
Genome,Synteny,Gene,Biology,Regulation of gene expression,Genomics,Bioinformatics,Multiple sequence alignment,Enhancer,Regulatory sequence
Journal
Volume
Issue
ISSN
18.0
9
1066-5277
Citations 
PageRank 
References 
0
0.34
4
Authors
3
Name
Order
Citations
PageRank
Emmanuel Mongin129680.42
Ken Dewar221.55
Mathieu Blanchette363162.65