Comparative promoter analysis and its application in analysis of PTH-regulated gene expression

Ping Qiu, Ling Qin, Richard P. Sorrentino, Jonathan R. Greene, Nicola Partridge, Luquan Wang

Research output: Contribution to journalArticlepeer-review

Abstract

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 CEBPDelta). 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.

Original languageEnglish (US)
Pages (from-to)1327-1336
Number of pages10
JournalJournal of Molecular Biology
Volume326
Issue number5
DOIs
StatePublished - Mar 7 2003

Keywords

  • Comparative analysis
  • Promoter
  • PTH
  • Transcription factor
  • TRANSFAC

ASJC Scopus subject areas

  • Virology

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