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Iron-Dependent Transcription Regulation
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DtxR
The diptheria toxin repressor (DtxR) controls expression
of the diptheria toxin gene in C. diptheria in an iron-dependent manner. We have
shown that repression of the toxin gene is dependent on the presence of Fe(II) but not Fe(III)
in the protein. Derepression of toxin synthesis is also observed after exposing DtxR to
NO. The exact mechanism of this derepression is still being examined. |
Fur
The Ferric Uptake Regulator (Fur) is an iron-dependent
repressor of gene transcription in gram-negative bacteria; however, little is known about the
biochemical details of repression by this protein. Although many of the genes controlled
by Fur are known to be involved in iron uptake, several others are of unknown function.
Like DtxR, Fur may be sensitive to NO. It may be part of an NO sensing and detoxification
pathway. |
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In the presence of metal, the repressor binds to the promoter/operator
region of a gene, blocking transcription of that gene. With loss of the metal, the repressor
dissociates from the DNA and transcription occurs.
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SREH
Histoplasma capsulatum is the causative agent of
histoplasmosis. Although distributed worldwide, H. capsulatum is classically
associated with the U.S. Midwest where >90% of the population is affected. Iron limitation
has been shown to be a specific mechanism of H. capsulatum infection control.
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SREH is a GATA-type transcription factor and putative regulator of iron
homeostasis in H. capsulatum. It contains two zinc finger proteins. |
GATA factors are zinc finger proteins |
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Bob Dylan: Poster Child for Histoplasmosis.
In 1997, legendary singer Bob Dylan was hospitalized for a severe case of histoplasmosis.
The infection had spread to the pericardium surrounding his heart. |
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Techniques Used:
Electrophoretic Mobility Shift Assays
Surface Plasmon Resonance
Electron Paramagnetic Resonance
Analytical Ultracentrifugation
Circular Dichroism
ICP-AES
In vitro Transcription/Translation |
Questions
How is iron involved in gene repression?
How does the redox state of iron effect gene repression?
How does NO effect gene repression, i.e. are these NO sensor proteins?
Do these repressor proteins control expression of an NO detoxification pathway?
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References
(1) Chao, LY.; Marletta, MA.; Rine, J. Sre1, an iron-modulated GATA DNA-binding protein of iron-uptake genes in the fungal pathogen Histoplasma capsulatum. Biochemistry 2008, 47, 7274-83.
(2) Spiering, MM; Ringe, D; Murphy, JR; Marletta, MA. Metal stoichiometry and functional studies of the diphtheria toxin repressor. Proc. Natl. Acad. Sci. USA 2003, 100, 3808-13.
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