Design of a combinatorial DNA microarray for protein-DNA interaction studies.
BACKGROUND
Discovery of precise specificity of transcription factors is an important step on the way to understanding the complex mechanisms of gene regulation in eukaryotes. Recently, double-stranded protein-binding microarrays were developed as a potentially scalable approach to tackle transcription factor binding site identification.


RESULTS
Here we present an algorithmic approach to experimental design of a microarray that allows for testing full specificity of a transcription factor binding to all possible DNA binding sites of a given length, with optimally efficient use of the array. This design is universal, works for any factor that binds a sequence motif and is not species-specific. Furthermore, simulation results show that data produced with the designed arrays is easier to analyze and would result in more precise identification of binding sites.


CONCLUSIONS
In this study, we present a design of a double stranded DNA microarray for protein-DNA interaction studies and show that our algorithm allows optimally efficient use of the arrays for this purpose. We believe such a design will prove useful for transcription factor binding site identification and other biological problems.
Mintseris
Julian
J
Boston University, Bioinformatics Program, Boston, MA, USA. julianm@bu.edu
Eisen
Michael B
MB
D024509:3' Flanking Region; D024506:5' Flanking Region; D000465:Algorithms; D001483:Base Sequence; D001665:Binding Sites; D019295:Computational Biology; D003198:Computer Simulation; D004247:DNA / Q000378:metabolism*; D015342:DNA Probes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D009841:Oligonucleotides / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D015342:DNA Probes; D004268:DNA-Binding Proteins; D009841:Oligonucleotides; C440829:RAP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; D004247:DNA