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Gene regulation

Modelling by building blocks

Nature Reviews Genetics volume 10, page 3 (2009)Cite this article

Thermodynamic models of gene expression are based on the assumption that the level of gene expression is proportional to the equilibrium probability that RNA polymerase is bound to the promoter of interest. These models have previously been used to describe gene expression in small sets of eukaryotic genes; however, there have been concerns that these models are subject to over-fitting owing to the small number of genomic promoters that have been studied in these systems. The use of synthetic gene promoters avoids this limitation — any promoter sequence can be created and analysed, thus allowing models to be assessed using most of the possible combinations of regulatory elements.

Cohen and colleagues constructed synthetic promoter libraries in the yeast Saccharomyces cerevisiae. Each promoter consisted of random combinations of three or four transcription-factor binding sites (or 'building blocks'), and its activity was assayed by monitoring the expression of a downstream reporter gene, yellow fluorescent protein (YFP). Over 2,800 promoters using combinations of 18 different building blocks were analysed — this allowed the authors to test their general thermodynamic model using many combinations of regulatory elements.

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References

ORIGINAL RESEARCH PAPER

  1. Gertz J. et al. Analysis of combinatorial cis-regulation in synthetic and genomic promoters. Nature 23 Nov 2008 (doi:10.1038/nature07521)

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FURTHER READING

  1. Boone C. et al. Exploring genetic interactions and networks with yeast. Nature Rev. Genet. 8, 437–449 (2007).

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Authors
  1. Meera Swami
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Swami, M. Modelling by building blocks. Nat Rev Genet 10, 3 (2009). https://doi.org/10.1038/nrg2510

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  • DOI: https://doi.org/10.1038/nrg2510

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