Statistical analysis of over-represented words in human promoter sequences

Nucleic Acids Res. 2004 Feb 12;32(3):949-58. doi: 10.1093/nar/gkh246. Print 2004.


The identification and characterization of regulatory sequence elements in the proximal promoter region of a gene can be facilitated by knowing the precise location of the transcriptional start site (TSS). Using known TSSs from over 5700 different human full-length cDNAs, this study extracted a set of 4737 distinct putative promoter regions (PPRs) from the human genome. Each PPR consisted of nucleotides from -2000 to +1000 bp, relative to the corresponding TSS. Since many regulatory regions contain short, highly conserved strings of less than 10 nucleotides, we counted eight-letter words within the PPRs, using z-scores and other related statistics to evaluate their over- and under-representation. Several over-represented eight-letter words have known biological functions described in the eukaryotic transcription factor database TRANSFAC; however, many did not. Besides calculating a P-value with the standard normal approximation associated with z-scores, we used two extra statistical controls to evaluate the significance of over-represented words. These controls have important implications for evaluating over- and under-represented words with z-scores.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Computer Simulation
  • Data Interpretation, Statistical
  • Genome, Human
  • Humans
  • Markov Chains
  • Promoter Regions, Genetic*
  • Transcription Factors / metabolism
  • Transcription Initiation Site


  • Transcription Factors