Nucleotides of transcription factor binding sites exert interdependent effects on the binding affinities of transcription factors
AUTOR(ES)
Bulyk, Martha L.
FONTE
Oxford University Press
RESUMO
We can determine the effects of many possible sequence variations in transcription factor binding sites using microarray binding experiments. Analysis of wild-type and mutant Zif268 (Egr1) zinc fingers bound to microarrays containing all possible central 3 bp triplet binding sites indicates that the nucleotides of transcription factor binding sites cannot be treated independently. This indicates that the current practice of characterizing transcription factor binding sites by mutating individual positions of binding sites one base pair at a time does not provide a true picture of the sequence specificity. Similarly, current bioinformatic practices using either just a consensus sequence, or even mononucleotide frequency weight matrices to provide more complete descriptions of transcription factor binding sites, are not accurate in depicting the true binding site specificities, since these methods rely upon the assumption that the nucleotides of binding sites exert independent effects on binding affinity. Our results stress the importance of complete reference tables of all possible binding sites for comparing protein binding preferences for various DNA sequences. We also show results suggesting that microarray binding data using particular subsets of all possible binding sites can be used to extrapolate the relative binding affinities of all possible full-length binding sites, given a known binding site for use as a starting sequence for site preference refinement.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=101241Documentos Relacionados
- Factors Influencing the Identification of Transcription Factor Binding Sites by Cross-Species Comparison
- DNA Replication Efficiency Depends on Transcription Factor-Binding Sites
- TRANSFAC: a database on transcription factors and their DNA binding sites.
- Adaptive evolution of transcription factor binding sites
- Multiple interdependent regulatory sites in the mouse c-fos promoter determine basal level transcription: cell type-specific effects.