Combining microarray and genomic data to predict DNA binding motifs

• Published in: Microbiology (Society for General Microbiology) 2005-10, Vol.151 (10), p.3197-3213
• Main Authors: Mao, Linyong, Mackenzie, Chris, Roh, Jung H, Eraso, Jesus M, Kaplan, Samuel, Resat, Haluk
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Base Sequence; Biological and medical sciences; Computational Biology - methods; Consensus Sequence; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Enhancer Elements, Genetic; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genetics; Genome, Bacterial; Microbiology; Molecular Sequence Data; Oligonucleotide Array Sequence Analysis; Photosynthesis; Repressor Proteins - chemistry; Repressor Proteins - genetics; Repressor Proteins - metabolism; Rhodobacter sphaeroides; Rhodobacter sphaeroides - genetics; Rhodobacter sphaeroides - metabolism; Sequence Analysis, DNA; Trans-Activators - chemistry; Trans-Activators - genetics; Trans-Activators - metabolism
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/mic.0.28167-0

1 Pacific Northwest National Laboratory, Computational Biology and Bioinformatics Group, PO Box 999, MS: K7-90, Richland, WA 99352, USA 2 Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center, Medical School, Houston, TX 77030, USA Correspondence Haluk Resat haluk.resat{at}pnl.gov The ability to detect regulatory elements within genome sequences is important in understanding how gene expression is controlled in biological systems. In this work, microarray data analysis is combined with genome sequence analysis to predict DNA sequences in the photosynthetic bacterium Rhodobacter sphaeroides that bind the regulators PrrA, PpsR and FnrL. These predictions were made by using hierarchical clustering to detect genes that share similar expression patterns. The DNA sequences upstream of these genes were then searched for possible transcription factor recognition motifs that may be involved in their co-regulation. The approach used promises to be widely applicable for the prediction of cis -acting DNA binding elements. Using this method the authors were independently able to detect and extend the previously described consensus sequences that have been suggested to bind FnrL and PpsR. In addition, sequences that may be recognized by the global regulator PrrA were predicted. The results support the earlier suggestions that the DNA binding sequence of PrrA may have a variable-sized gap between its conserved block elements. Using the predicted DNA binding sequences, a whole-genome-scale analysis was performed to determine the relative importance of the interplay between the three regulators PpsR, FnrL and PrrA. Results of this analysis showed that, compared to the regulation by PpsR and FnrL, a much larger number of genes are candidates to be regulated by PrrA. The study demonstrates by example that integration of multiple data types can be a powerful approach for inferring transcriptional regulatory patterns in microbial systems, and it allowed the detection of photosynthesis-related regulatory patterns in R. sphaeroides . Abbreviations: CHPC, cluster with high photosynthesis content