title: Transcriptional regulation of Mycobacterium tuberculosis hupB gene expression.
abstract: The influence of iron levels on the transcription of the hupB gene in Mycobacterium tuberculosis is the focus of this study. Studies in our laboratory showed HupB to be co-expressed with the two siderophores in low-iron organisms. Mycobactin biosynthesis is repressed by the IdeR-Fe(2+) complex that binds the IdeR box in the mbtB promoter. Recently, we demonstrated the positive regulatory effect of HupB on mycobactin biosynthesis by demonstrating its binding to a 10 bp HupB box in the mbtB promoter. Earlier, we observed that HupB, expressed maximally in low-iron media (0.02 µg Fe ml(-1); 0.36 µM Fe) was still detectable at 8 µg Fe ml(-1) (144 µM Fe) when the siderophores were absent and complete repression was seen only at 12 µg Fe ml(-1) (216 µM Fe). In this study, we observed elevated levels of hupB transcripts in iron-limited organisms. IdeR, and not FurA, functioned as the iron regulator, by binding to two IdeR boxes in the hupB promoter. Interestingly, the 10 bp HupB box, first reported in the mbtB promoter, was identified in the hupB promoter. Using DNA footprinting and electrophoretic mobility shift assays, we demonstrated the functionality of the HupB box and the two IdeR boxes. The high hupB transcript levels expressed by the organism and the in vitro protein-DNA interaction studies led us to hypothesize the sequence of events occurring in response to changes in the intracellular iron concentration, emphasizing the roles played by IdeR and HupB in iron homeostasis.
authors.affiliation: Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Prof. C.R. Rao Road, Gachibowli, Hyderabad 500046, India.
authors.forename: Satya Deo
authors.initials: SD
authors.lastname: Pandey
authors.affiliation: Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Prof. C.R. Rao Road, Gachibowli, Hyderabad 500046, India.
authors.forename: Mitali
authors.initials: M
authors.lastname: Choudhury
authors.affiliation: Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Prof. C.R. Rao Road, Gachibowli, Hyderabad 500046, India.
authors.forename: Manjula
authors.initials: M
authors.lastname: Sritharan
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D006657:Histones; C510666:HupB protein, Mycobacterium tuberculosis; C096348:IdeR protein, Mycobacterium tuberculosis; D012097:Repressor Proteins; D007501:Iron