Abstract
Data obtained with advanced imaging techniques, chromosome conformation capture methods, bioinformatics and molecular genetics, together with insights from polymer physics and mechanobiology, are helping to refine our understanding of the spatiotemporal organization of the bacterial nucleoid and its gene expression programmes. Here, I discuss the proposal that, in addition to DNA topology and nucleoid-associated proteins, gene regulation is an important organizing principle of nucleoid architecture.
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05 April 2013
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Acknowledgements
The author thanks R. L. Gourse and R. T. Dame for helpful discussions, and the three anonymous reviewers for insightful comments. The author also thanks N. Ní Bhriain for comments on the manuscript and M. J. Dorman for assistance with computation. This work was supported by a grant from Science Foundation Ireland.
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FURTHER INFORMATION
Glossary
- Chromatin immunoprecipitation followed by microarray
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(ChIP–chip). A method that allows the binding sites for a specific protein to be identified throughout a genome in vivo. The protein of interest is crosslinked to DNA in living bacteria with formaldehyde, and the genomic DNA is extracted and then sonicated to achieve a desired average DNA fragment length. An antibody specific for the protein of interest (or for an epitope tag that has been attached to the protein by genetic engineering) is used to precipitate the protein–DNA complex. The crosslinks are then reversed, the released DNA is fluorescently tagged, and its genomic location is identified using a DNA microarray.
- Chromosome conformational capture
-
(3C). A technique that identifies physical interactions between parts of the genome (specifically, interactions that would not be predictable from a survey of the DNA sequence alone). Macromolecules are chemically crosslinked in living cells, and then the DNA is extracted, digested with a restriction enzyme and subjected to intramolecular ligation. PCR is used to detect novel junctions in the ligated DNA, which are predicted to arise from the close proximity of the now-joined sequences in the folded nucleoid. A chromatin immunoprecipitation step can be added to study novel interactions that depend on a specific protein, such as a nucleoid-associated protein.
- Chromosome conformational capture carbon copy
-
(5C). A chromosome conformational capture (3C) library is first constructed, and then multiplex primers with universal primer extensions are annealed to the novel junctions in the library and ligated together. The 3C junctions serve as templates to guide the perfect ligation of the primers. These can then be used in microarrays or subjected to high-throughput sequencing to identify the DNA forming the junction.
- Dps
-
(DNA protection during starvation). A nucleoid-associated protein that is expressed in stationary phase cultures (or in cultures experiencing oxidative stress) and is thought to protect the DNA from damage.
- Fis
-
(Factor-for-inversion stimulation). A nucleoid-associated protein that is expressed in early exponential phase cultures, organizes the local DNA topology and modulates transcription.
- H-NS
-
(Histone-like, nucleoid-structuring protein). A nucleoid-associated protein with a preference for binding to AT-rich DNA. H-NS is expressed at all stages of growth, silences the transcription of hundreds of genes and organizes nucleoid structure.
- HU
-
A nucleoid-associated protein with a general DNA-binding and DNA-compacting activity.
- IHF
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(Integration host factor). A paralogue of HU with site-specific DNA-binding and DNA-bending activity.
- Macrodomains
-
Genetically defined large-scale chromosomal segments that are unlikely to undergo recombination with each other because the resulting rearrangements are detrimental to the survival of the bacterium. The Escherichia coli chromosome has four macrodomains (Ori, Ter, Left and Right) and two so-called non-structured regions (NS-left and NS-right).
- Microdomain
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A topologically independent 10–12 kb loop that coexists with other microdomains within the macrodomain superstructure of the Escherichia coli genome. There are around 400 microdomain loops in the genome.
- Nucleoid-associated proteins
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(NAPs). Low-molecular-mass, abundant DNA-binding proteins that are thought to act as architectural components within the nucleoid and to modulate gene expression. Escherichia coli has at least 12 distinct NAPs.
- Replichores
-
The two arms of the circular chromosome along which bidirectional DNA replication occurs. The right (or clockwise) replichore and the left (or anticlockwise) replichore each extend, in opposite directions, from the origin of chromosome replication (oriC in Escherichia coli) within the Ori macrodomain to the terminus of replication within the Ter macrodomain.
- Topoisomerase
-
An enzyme that alters the linking number of the DNA by cutting, strand passage and religation.
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Dorman, C. Genome architecture and global gene regulation in bacteria: making progress towards a unified model?. Nat Rev Microbiol 11, 349–355 (2013). https://doi.org/10.1038/nrmicro3007
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DOI: https://doi.org/10.1038/nrmicro3007
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