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Nucleic Acids Research Advance Access originally published online on February 14, 2008
Nucleic Acids Research 2008 36(6):2032-2046; doi:10.1093/nar/gkn046
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Nucleic Acids Research, 2008, Vol. 36, No. 6 2032-2046
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genomics

Transcriptional regulation of NAD metabolism in bacteria: genomic reconstruction of NiaR (YrxA) regulon

Dmitry A. Rodionov1,2,*, Xiaoqing Li1, Irina A. Rodionova1, Chen Yang1, Leonardo Sorci1, Etienne Dervyn3, Dariusz Martynowski4, Hong Zhang4, Mikhail S. Gelfand2 and Andrei L. Osterman1,5

1Burnham Institute for Medical Research, La Jolla, CA 92037, USA, 2Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow 127994, Russia, 3Génétique Microbienne, INRA, 78352 Jouy-en-Josas, France, 4Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 and 5Fellowship for Interpretation of Genomes, Burr Ridge, IL 60527, USA

*To whom correspondence should be addressed. Tel: +1 858 646 3100; Fax: +1 858 795 5249; Email: rodionov{at}burnham.org

Received December 5, 2007. Revised January 18, 2008. Accepted January 24, 2008.

A comparative genomic approach was used to reconstruct transcriptional regulation of NAD biosynthesis in bacteria containing orthologs of Bacillus subtilis gene yrxA, a previously identified niacin-responsive repressor of NAD de novo synthesis. Members of YrxA family (re-named here NiaR) are broadly conserved in the Bacillus/Clostridium group and in the deeply branching Fusobacteria and Thermotogales lineages. We analyzed upstream regions of genes associated with NAD biosynthesis to identify candidate NiaR-binding DNA motifs and assess the NiaR regulon content in these species. Representatives of the two distinct types of candidate NiaR-binding sites, characteristic of the Firmicutes and Thermotogales, were verified by an electrophoretic mobility shift assay. In addition to transcriptional control of the nadABC genes, the NiaR regulon in some species extends to niacin salvage (the pncAB genes) and includes uncharacterized membrane proteins possibly involved in niacin transport. The involvement in niacin uptake proposed for one of these proteins (re-named NiaP), encoded by the B. subtilis gene yceI, was experimentally verified. In addition to bacteria, members of the NiaP family are conserved in multicellular eukaryotes, including human, pointing to possible NaiP involvement in niacin utilization in these organisms. Overall, the analysis of the NiaR and NrtR regulons (described in the accompanying paper) revealed mechanisms of transcriptional regulation of NAD metabolism in nearly a hundred diverse bacteria.


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