Abstract
Transcription initiation is the first step in the regulation of gene expression. Promoters are the regions of genomic DNA where transcription initiation machinery assembles and are generally characterized by presence of short nucleotide sequence motifs like TATA-box, Inr element, BRE, etc. However, apart from these motifs, promoter regions have been reported to have structural properties, such as lower stability, lesser bendability and more curvature compared to other genomic regions. Interestingly, these properties are conserved from archaea to mammals, with little differences. Several algorithms have been developed to differentiate promoter regions from non promoters, using DNA structural properties. Here we show that, in E. coli and S. cerevisiae, genes with different experimentally determined expression levels, differ in their structural features. Promoters of highly expressed or less responsive genes are less stable, less bendable and more curved compared to promoters of lowly expressed or more responsive genes. This suggests that these structural properties can be used to design promoters to modulate gene expression.
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Notes
- 1.
Bendability and curvature are cooperative in nature, whereas stability is only restricted to nearest neighbor effects.
- 2.
- 3.
The terms bendability, rigidity and flexibility have been used interchangeably. DNA flexibility is of two types, torsional flexibility (due to variations in twist about the axis) and bending flexibility (or bendability, due to variations in roll, tilt, slide and shift). In present context rigidity or flexibility refers to only bending flexibility.
- 4.
Curvature values shown here are calculated using BMHT dinucleotide step parameters (Bolshoy et al. 1991) and in-house software NUCRADGEN (http://nucleix.mbu.iisc.ernet.in/nucradgen/index.htm).
- 5.
A-tracts consist of stretches of minimum four consecutive A:T base pairs without a flexible TA step.
- 6.
- 7.
Responsiveness is the gene expression variability measured from curated datasets representing various conditions. Responsiveness data for S. cerevisiae was downloaded from (Choi and Kim 2009).
- 8.
The number of promoter sequences considered for this analysis are 100Â in the datasets corresponding to highest and lowest gene expression in case of E. coli. The two datasets corresponding to low and high responsiveness contaians 200 sequences for S. cerevisiae.
- 9.
The trinucleotides sorted using NPP model are not according to absolute flexibility values, but on the basis of rotational preference for minor or major groove.
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Acknowledgements
AK acknowledges CSIR, INDIA for scholarship. MB is a recipient of J. C. Bose National Fellowship of DST, India. We thank Asmita Gupta for assistance in the preparation of Fig. 13.1.
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Yella, V., Kumar, A., Bansal, M. (2015). DNA Structure and Promoter Engineering. In: Singh, V., Dhar, P. (eds) Systems and Synthetic Biology. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9514-2_13
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