DNA Structure and Promoter Engineering
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.
KeywordsPromoter engineering DNA structural properties DNA duplex stability DNA bendability Intrinsic curvature NUCRADGEN Transcription factor binding sites (TFBSs)
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.
- Carninci P, Sandelin A, Lenhard B, Katayama S, Shimokawa K, Ponjavic J, Semple CA, Taylor MS, Engstrom PG, Frith MC, Forrest AR, Alkema WB, Tan SL, Plessy C, Kodzius R, Ravasi T, Kasukawa T, Fukuda S, Kanamori-Katayama M, Kitazume Y, Kawaji H, Kai C, Nakamura M, Konno H, Nakano K, Mottagui-Tabar S, Arner P, Chesi A, Gustincich S, Persichetti F, Suzuki H, Grimmond SM, Wells CA, Orlando V, Wahlestedt C, Liu ET, Harbers M, Kawai J, Bajic VB, Hume DA, Hayashizaki Y (2006) Genome-wide analysis of mammalian promoter architecture and evolution. Nat Genet 38(6):626–635PubMedCrossRefGoogle Scholar
- Falconi M, Colonna B, Prosseda G, Micheli G, Gualerzi CO (1998) Thermoregulation of Shigella and Escherichia coli EIEC pathogenicity. A temperature-dependent structural transition of DNA modulates accessibility of virF promoter to transcriptional repressor H-NS. EMBO J 17(23):7033–7043PubMedCentralPubMedCrossRefGoogle Scholar
- Gama-Castro S, Salgado H, Peralta-Gil M, Santos-Zavaleta A, Muniz-Rascado L, Solano-Lira H, Jimenez-Jacinto V, Weiss V, Garcia-Sotelo JS, Lopez-Fuentes A, Porron-Sotelo L, Alquicira-Hernandez S, Medina-Rivera A, Martinez-Flores I, Alquicira-Hernandez K, Martinez-Adame R, Bonavides-Martinez C, Miranda-Rios J, Huerta AM, Mendoza-Vargas A, Collado-Torres L, Taboada B, Vega-Alvarado L, Olvera M, Olvera L, Grande R, Morett E, Collado-Vides J (2011) RegulonDB version 7.0: transcriptional regulation of Escherichia coli K-12 integrated within genetic sensory response units (Gensor Units). Nucleic Acids Res 39(Database issue):98–105CrossRefGoogle Scholar
- Wakaguri H, Yamashita R, Suzuki Y, Sugano S, Nakai K (2008) DBTSS: database of transcription start sites, progress report 2008. Nucleic Acids Res 36(Database issue):97–101Google Scholar