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Promoters maintain their relative activity levels under different growth conditions

Leeat Keren, Ora Zackay, Maya Lotan‐Pompan, Uri Barenholz, Erez Dekel, Vered Sasson, Guy Aidelberg, Anat Bren, Danny Zeevi, Adina Weinberger, Uri Alon, Ron Milo, Eran Segal

Author Affiliations

  1. Leeat Keren1,2,3,
  2. Ora Zackay1,2,
  3. Maya Lotan‐Pompan1,2,
  4. Uri Barenholz3,
  5. Erez Dekel2,
  6. Vered Sasson2,
  7. Guy Aidelberg2,
  8. Anat Bren2,
  9. Danny Zeevi1,2,
  10. Adina Weinberger1,2,
  11. Uri Alon2,
  12. Ron Milo3 and
  13. Eran Segal*,1,2
  1. 1 Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
  2. 2 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
  3. 3 Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel
  1. *Corresponding author. Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel. Tel.:+972 89346488; Fax:+972 89346488; E‐mail: eran.segal{at}weizmann.ac.il
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Abstract

Most genes change expression levels across conditions, but it is unclear which of these changes represents specific regulation and what determines their quantitative degree. Here, we accurately measured activities of ∼900 S. cerevisiae and ∼1800 E. coli promoters using fluorescent reporters. We show that in both organisms 60–90% of promoters change their expression between conditions by a constant global scaling factor that depends only on the conditions and not on the promoter's identity. Quantifying such global effects allows precise characterization of specific regulation—promoters deviating from the global scale line. These are organized into few functionally related groups that also adhere to scale lines and preserve their relative activities across conditions. Thus, only several scaling factors suffice to accurately describe genome‐wide expression profiles across conditions. We present a parameter‐free passive resource allocation model that quantitatively accounts for the global scaling factors. It suggests that many changes in expression across conditions result from global effects and not specific regulation, and provides means for quantitative interpretation of expression profiles.

Synopsis

Libraries of S. cerevisiae and E. coli promoter reporters measured under different conditions reveal scaling relationships between expression profiles across conditions and suggest that most changes in activity are due to global effects.

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  • Between any two conditions, the activity of most promoters changes by a constant global scaling factor that depends only on the conditions and not on the promoter's identity.

  • The value of the global scaling factor between any two conditions corresponds to the change in growth rate and magnitude of the condition‐specific response.

  • When specific groups of genes are activated, they also tend to change according to scaling factors, changing the degree to which the entire group is activated, while preserving the ratios between genes within the group.

  • Altogether, a handful of scaling factors are sufficient for quantitatively describing genome‐wide expression profiles across conditions.

Mol Syst Biol. 9: 701

  • Received August 5, 2013.
  • Accepted September 27, 2013.
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This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.

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