Comparative promoter analysis and its application in analysis of PTH-regulated gene expression.
Taking advantage of the "working draft" of the human genome and the MIT shotgun assembly of the mouse genome, we performed a comparative promoter analysis of human RefSeq mRNA (sequences from GenBank's RefSeq database). By combining this analysis with a transcription factor (TF) binding site analysis using a TRANSFAC position weight matrix (PWM) search, 86% of non-specific TF sites were removed. Using a set of genes that are regulated by parathyroid hormone (PTH), a statistical analysis was performed on the conserved TF binding sites among a set of eight human and mouse genes. From among the eight genes tested, we obtained a set of 31 TFs, suggesting possible roles for associated genes in PTH-mediated pathways. All three known PTH-responsive TFs (AP1, RUNX2, CREB) were correctly predicted by this analysis as well as two other potential TFs (VDR and CEBP Delta). Additionally, a model was made to describe the TF site characteristic module of PTH-regulated genes. This model was then used to search all human RefSeq gene promoters with established human-mouse ortholog relationships to identify other PTH-regulated genes. This comparative approach combined with statistical analysis proved to be sufficiently specific to decipher critical TFs involved in PTH-regulated pathways.
Qiu
Ping
P
Bioinformatics Group and Discovery Technology Department, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. ping.qiu@spcorp.com
Qin
Ling
L
Sorrentino
Richard P
RP
Greene
Jonathan R
JR
Wang
Luquan
L
Partridge
Nicola C
NC
D000465:Algorithms; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D016384:Consensus Sequence; D018983:DNA Footprinting; D016208:Databases, Factual; D005786:Gene Expression Regulation / Q000187:drug effects*; D016678:Genome; D006801:Humans; D051379:Mice; D008954:Models, Biological; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D018016:Receptors, Parathyroid Hormone; D020218:Response Elements; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D010281:Parathyroid Hormone; D018016:Receptors, Parathyroid Hormone; D014157:Transcription Factors