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Nucleic Acids Research 2005 33(16):5156-5171; doi:10.1093/nar/gki817
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Published online 12 September 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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Genomics

Comparative genomics analysis of NtcA regulons in cyanobacteria: regulation of nitrogen assimilation and its coupling to photosynthesis

Zhengchang Su, Victor Olman, Fenglou Mao and Ying Xu*

Bioinformatics Institute and Department of Biochemistry and Molecular Biology, University of Georgia Athens, GA 30602, USA

*To whom correspondence should be addressed. Tel: 706 542 9779; Fax: 706 542 9751; Email: xyn{at}bmb.uga.edu

Received March 30, 2005. Revised July 8, 2005. Accepted August 19, 2005.

We have developed a new method for prediction of cis-regulatory binding sites and applied it to predicting NtcA regulated genes in cyanobacteria. The algorithm rigorously utilizes concurrence information of multiple binding sites in the upstream region of a gene and that in the upstream regions of its orthologues in related genomes. A probabilistic model was developed for the evaluation of prediction reliability so that the prediction false positive rate could be well controlled. Using this method, we have predicted multiple new members of the NtcA regulons in nine sequenced cyanobacterial genomes, and showed that the false positive rates of the predictions have been reduced on an average of 40-fold compared to the conventional methods. A detailed analysis of the predictions in each genome showed that a significant portion of our predictions are consistent with previously published results about individual genes. Intriguingly, NtcA promoters are found for many genes involved in various stages of photosynthesis. Although photosynthesis is known to be tightly coordinated with nitrogen assimilation, very little is known about the underlying mechanism. We postulate for the fist time that these genes serve as the regulatory points to orchestrate these two important processes in a cyanobacterial cell.


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