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Rv3133c/ dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis
Open accessAbstract
Summary: Unlike many pathogens that are overtly harmful to their hosts, Mycobacterium tuberculosis can persist for years within humans in a clinically latent state. Latency is often linked to hypoxic conditions within the host. Among M. tuberculosis genes induced by hypoxia is a putative transcription factor, Rv3133c/DosR. We performed targeted disruption of this locus followed by transcriptome analysis of wild‐type and mutant bacilli. Nearly all the genes powerfully regulated by hypoxia require Rv3133c/DosR for their induction. Computer analysis identified a consensus motif, a variant of which is located upstream of nearly all M. tuberculosis genes rapidly induced by hypoxia. Further, Rv3133c/DosR binds to the two copies of this motif upstream of the hypoxic response gene alpha‐crystallin. Mutations within the binding sites abolish both Rv3133c/DosR binding as well as hypoxic induction of a downstream reporter gene. Also, mutation experiments with Rv3133c/DosR confirmed sequence‐based predictions that the C‐terminus is responsible for DNA binding and that the aspartate at position 54 is essential for function. Together, these results demonstrate that Rv3133c/DosR is a transcription factor of the two‐component response regulator class, and that it is the primary mediator of a hypoxic signal within M. tuberculosis .
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“DosR has been shown to act as a transcriptional regulator, which is responsible for the induction of nearly all hypoxia-induced genes of M. tuberculosis (96).”
From Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria (2014) · cites this paper as [96]
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Metadata
- Authors
- Park, H., Guinn, K. M., Harrell, M. I., Liao, R., Voskuil, M. I., Tompa, M., Schoolnik, G. K., & Sherman, D. R.
- Affiliations
- University of Washington (US)
- Stanford Medicine (US)
- Corresponding author
- Sherman, David R.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2003-04-09
- Volume
- 48
- Issue
- 3
- Pages
- 833-843
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- PMC
- PMC1992516
- OpenAlex
- W2120842435
- Cited by
- 712
- References
- 61
- Citations by year
- 2026: 20 · 2025: 22 · 2024: 20 · 2023: 26 · 2022: 24 · 2021: 37 · 2020: 34 · 2019: 35 · 2018: 28 · 2017: 33 · 2016: 30 · 2015: 31 · 2014: 46 · 2013: 32 · 2012: 41
- FWCI
- 14.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation (9974498)
- National Institutes of Health
- National Human Genome Research Institute (HG02602-01, R01HG002602)
- National Institute of Allergy and Infectious Diseases (R01AI044826, AI-44826, R21AI047744, AI47744, R01AI047744)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Keywords
- Mycobacterium tuberculosis, transcription factors, hypoxia response, hypoxia, transcriptional regulation, two-component response regulator, DNA-binding motifs, alpha-crystallin, latent tuberculosis infection, gene induction
- MeSH terms
- Hypoxia, Aspartic Acid, Bacterial Proteins, Humans, Mycobacterium tuberculosis, Oxygen, Protein Binding, Regulatory Sequences, Nucleic Acid, Transcription Factors, Tuberculosis, Gene Expression Regulation, Bacterial, Genes, Reporter, Gene Targeting, Oligonucleotide Array Sequence Analysis
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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