We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Evolution of transcription factor binding sites in Mammalian gene regulatory regions: conservation and turnover.
- Authors
Dermitzakis, Emmanouil T; Clark, Andrew G
- Abstract
Comparisons between human and rodent DNA sequences are widely used for the identification of regulatory regions (phylogenetic footprinting), and the importance of such intergenomic comparisons for promoter annotation is expanding. The efficacy of such comparisons for the identification of functional regulatory elements hinges on the evolutionary dynamics of promoter sequences. Although it is widely appreciated that conservation of sequence motifs may provide a suggestion of function, it is not known as to what proportion of the functional binding sites in humans is conserved in distant species. In this report, we present an analysis of the evolutionary dynamics of transcription factor binding sites whose function had been experimentally verified in promoters of 51 human genes and compare their sequence to homologous sequences in other primate species and rodents. Our results show that there is extensive divergence within the nucleotide sequence of transcription factor binding sites. Using direct experimental data from functional studies in both human and rodents for 20 of the regulatory regions, we estimate that 32%-40% of the human functional sites are not functional in rodents. This is evidence that there is widespread turnover of transcription factor binding sites. These results have important implications for the efficacy of phylogenetic footprinting and the interpretation of the pattern of evolution in regulatory sequences.
- Publication
Molecular biology and evolution, 2002, Vol 19, Issue 7, p1114
- ISSN
0737-4038
- Publication type
Journal Article
- DOI
10.1093/oxfordjournals.molbev.a004169