Affiliations: Aventis Pharmaceuticals Inc., Route 202/206,
Bridgewater, NJ 08807, USA | Portland State University, Portland, OR 97207,
USA | Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
11724, USA
Abstract: DNA-binding transcription factors play a central role in
transcription regulation, and the annotation of transcription-factor binding
sites in upstream regions of human genes is essential for building a
genome-wide regulatory network. We describe methodology to accurately predict
the transcription-factor binding sites in the proximal-promoter region of
function-specific genes. In order to increase the accuracy of transcription
factor binding-site prediction, we rely on recent genome sequence data, known
transcription factor binding-site matrices, and Gene Ontology
biological-function-based gene classification. Using TRANSFAC
position-frequency matrices, we detected individual and cooperating
transcription-factor binding sites in proximal promoters of ENSEMBL annotated
human genes. We used the over representation of detected binding sites in the
proximal promoters as compared to the second exons to control specificity. We
confirmed the majority of transcription-factor binding sites predicted in
proximal promoters of immune-response genes with evidence from existing
literature. We validated the predicted cooperation between transcription
factors NF-κB and IRF in the regulation of gene
expression with microarray transcript profiling data and literature-derived
protein-protein interaction network. We also identified over-represented
individual and pairs of transcription-factor binding sites in the proximal
promoters of each Gene Ontology biological-process gene group. Our tools and
analysis provide a new resource for deciphering transcription regulation in
different biological paradigms.
