Trascriptional regolatory code of a eukaryotic genome

Vedi la traduzione: codice-regolativo-trascrizionale-genoma-eucariotico


We have constructed an initial map of yeast’s transcriptional regulatory code by identifying the sequence elements that are bound by regulators under various conditions and that are conserved among Saccharomyces species. The organization of regulatory elements in promoters and the environment-dependent use of these elements by regulators are discussed. We find that environment-specific use of regulatory elements predicts mechanistic models for the function of a large population of yeast’s transcriptional regulators.

The vast majority (74%) of the transcriptional regulator binding sites lie between 100 and 500 bp upstream of the protein-coding sequence, far more than would be expected at random (53%). condition. Regions further than 500 bp upstream contain fewer binding sites than would be expected at random. It seems that yeast transcriptional regulators function at short distances along the linear DNA, a property that reduces the potential for inappropriate activation of nearby genes.

Promoter classification

  1. The presence of a DNA binding site for a single regulator is the simplest promoter architecture and, as might be expected, we found that sets of genes with this feature are often involved in a common biological function.
  2. A second type of promoter architecture consists of repeats of a particular binding site sequence. Repeated binding sites have been shown to be necessary for stable binding by the regulator Dal80 (ref. 15). This repetitive promoter architecture can also permit a graded transcriptional response, as has been observed for the HIS4 gene16. Several regulators, including Dig1, Mbp1 and Swi6, show a statistically significant preference for repetitive motifs (Supplementary Table 5).
  3. A third class of promoter contains binding sites for multiple different regulators. This promoter arrangement implies that the gene might be subject to combinatorial regulation, and we expect that in many cases the various regulators can be used to execute differential responses to varied growth conditions.
  4. In the fourth type of promoter architecture we discuss here, binding sites for specific pairs of regulators occur more frequently within the same promoter regions than would be expected by chance (Supplementary Table 6). This ‘co-occurring’ motif architecture implies that the two regulators interact physically or have related functions at multiple genes.
Bibliography
1. NATURE | VOL 431 | 2 SEPTEMBER 2004 | www.nature.com/nature, Transcriptional regulatory code of a eukaryotic genome, Christopher T. Harbison, D. Benjamin Gordon, Tong Ihn Lee, Nicola J. Rinaldi, Kenzie D. Macisaac, Timothy W. Danford, Nancy M. Hannett, Jean-Bosco Tagne, David B. Reynolds, Jane Yoo, Ezra G. Jennings, Julia Zeitlinger, Dmitry K. Pokholok, Manolis Kellis, P. Alex Rolfe, Ken T. Takusagawa, Eric S. Lander, David K. Gifford, Ernest Fraenkel & Richard A. Young
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