TY - JOUR
T1 - Transcriptional regulation of NAD metabolism in bacteria
T2 - Genomic reconstruction of NiaR (YrxA) regulon
AU - Rodionov, Dmitry A.
AU - Li, Xiaoqing
AU - Rodionova, Irina A.
AU - Yang, Chen
AU - Sorci, Leonardo
AU - Dervyn, Etienne
AU - Martynowski, Dariusz
AU - Zhang, Hong
AU - Gelfand, Mikhail S.
AU - Osterman, Andrei L.
N1 - Funding Information:
This work was partially supported by grants from National Institute of Allergy and Infectious Deseases (NIAID) ‘Genomics of Coenzyme Metabolism in Bacterial Pathogens’ (1-R01-AI066244-01A2 to A.O.); and by the Program ‘Molecular and Cellular Biology’ of the Russian Academy of Sciences to M.G.. M.G. is a Howard Hughes International Research Scholar. Funding to pay the Open Access publication charges for this article was provided by National Institute of Health research grant 1-R01-AI066244-01A2.
PY - 2008/4
Y1 - 2008/4
N2 - 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.
AB - 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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U2 - 10.1093/nar/gkn046
DO - 10.1093/nar/gkn046
M3 - Article
C2 - 18276644
AN - SCOPUS:41849131511
SN - 0305-1048
VL - 36
SP - 2032
EP - 2046
JO - Nucleic acids research
JF - Nucleic acids research
IS - 6
ER -