RT Journal
A1 Blanchette, Mathieu
A1 Bataille, Alain R.
A1 Chen, Xiaoyu
A1 Poitras, Christian
A1 Laganière, Josée
A1 Lefèbvre, Céline
A1 Deblois, Geneviève
A1 Giguère, Vincent
A1 Ferretti, Vincent
A1 Bergeron, Dominique
A1 Coulombe, Benoit
A1 Robert, François
T1 Genome-wide computational prediction of transcriptional regulatory modules reveals new insights into human gene expression
JF Genome Research 
JO Genome Research 
YR 2006 
FD May 01 
VO 16 
IS 5 
SP 656 
OP 668 
DO 10.1101/gr.4866006 
UL http://genome.cshlp.org/content/16/5/656.abstract 
AB The identification of regulatory regions is one of the most important and challenging problems toward the functional annotation of the human genome. In higher eukaryotes, transcription-factor (TF) binding sites are often organized in clusters called cis-regulatory modules (CRM). While the prediction of individual TF-binding sites is a notoriously difficult problem, CRM prediction has proven to be somewhat more reliable. Starting from a set of predicted binding sites for more than 200 TF families documented in Transfac, we describe an algorithm relying on the principle that CRMs generally contain several phylogenetically conserved binding sites for a few different TFs. The method allows the prediction of more than 118,000 CRMs within the human genome. A subset of these is shown to be bound in vivo by TFs using ChIP-chip. Their analysis reveals, among other things, that CRM density varies widely across the genome, with CRM-rich regions often being located near genes encoding transcription factors involved in development. Predicted CRMs show a surprising enrichment near the 3′ end of genes and in regions far from genes. We document the tendency for certain TFs to bind modules located in specific regions with respect to their target genes and identify TFs likely to be involved in tissue-specific regulation. The set of predicted CRMs, which is made available as a public database called PReMod (http://genomequebec.mcgill.ca/PReMod), will help analyze regulatory mechanisms in specific biological systems.