title: Transcriptional regulation of NAD metabolism in bacteria: genomic reconstruction of NiaR (YrxA) regulon.
abstract: 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.
authors.affiliation: Burnham Institute for Medical Research, La Jolla, CA 92037, USA. rodionov@burnham.org
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Rodionov
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Li
authors.forename: Irina A
authors.initials: IA
authors.lastname: Rodionova
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.forename: Leonardo
authors.initials: L
authors.lastname: Sorci
authors.forename: Etienne
authors.initials: E
authors.lastname: Dervyn
authors.forename: Dariusz
authors.initials: D
authors.lastname: Martynowski
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Mikhail S
authors.initials: MS
authors.lastname: Gelfand
authors.forename: Andrei L
authors.initials: AL
authors.lastname: Osterman
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D023281:Genomics; D026901:Membrane Transport Proteins / Q000145:classification / Q000235:genetics; D009243:NAD / Q000378:metabolism*; D009525:Niacin / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D018085:Regulon; D012097:Repressor Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020124:Thermotoga maritima / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D012097:Repressor Proteins; D009243:NAD; D009525:Niacin