Evolution of Transcription Factor Binding Sites in Mammalian Gene Regulatory Regions: Conservation and Turnover

@article{citeulike:1045001, 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.}, author = {Dermitzakis, Emmanouil T. and Clark, Andrew G. }, citeulike-article-id = {1045001}, comment = {1. 51 gene regulatory regions 2. only study sequence divergence. no motif model is applied. 3. variations in binding sites between human and macaque is not homogeneously distributed but rather concentrated in a few sites.}, journal = {Mol Biol Evol}, keywords = {binding\_sites\_turnover, cis\_regulatory\_elements}, month = {July}, number = {7}, pages = {1114--1121}, posted-at = {2007-12-09 16:53:51}, priority = {5}, title = {Evolution of Transcription Factor Binding Sites in Mammalian Gene Regulatory Regions: Conservation and Turnover}, url = {http://mbe.oxfordjournals.org/cgi/content/abstract/19/7/1114}, volume = {19}, year = {2002} }

TY - JOUR ID - citeulike:1045001 L3 - citeulike-article-id:1045001 TI - Evolution of Transcription Factor Binding Sites in Mammalian Gene Regulatory Regions: Conservation and Turnover JF - Mol Biol Evol VL - 19 IS - 7 SP - 1114 EP - 1121 N2 - 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. KW - binding_sites_turnover KW - cis_regulatory_elements N1 - 1. 51 gene regulatory regions 2. only study sequence divergence. no motif model is applied. 3. variations in binding sites between human and macaque is not homogeneously distributed but rather concentrated in a few sites. AU - Dermitzakis, Emmanouil AU - Clark, Andrew PY - 2002/07/01/ UR - http://mbe.oxfordjournals.org/cgi/content/abstract/19/7/1114 ER -