Large-scale genetic perturbations reveal regulatory networks and an abundance of gene-specific repressors

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Patrick Kemmeren - , University Medical Center (UMC) Utrecht (Author)
  • Katrin Sameith - , University Medical Center (UMC) Utrecht (Author)
  • Loes A L van de Pasch - , University Medical Center (UMC) Utrecht (Author)
  • Joris J Benschop - , University Medical Center (UMC) Utrecht (Author)
  • Tineke L Lenstra - , University Medical Center (UMC) Utrecht (Author)
  • Thanasis Margaritis - , University Medical Center (UMC) Utrecht (Author)
  • Eoghan O'Duibhir - , University Medical Center (UMC) Utrecht (Author)
  • Eva Apweiler - , University Medical Center (UMC) Utrecht (Author)
  • Sake van Wageningen - , University Medical Center (UMC) Utrecht (Author)
  • Cheuk W Ko - , University Medical Center (UMC) Utrecht (Author)
  • Sebastiaan van Heesch - , University Medical Center (UMC) Utrecht (Author)
  • Mehdi M Kashani - , University Medical Center (UMC) Utrecht (Author)
  • Giannis Ampatziadis-Michailidis - , University Medical Center (UMC) Utrecht (Author)
  • Mariel O Brok - , University Medical Center (UMC) Utrecht (Author)
  • Nathalie A C H Brabers - , University Medical Center (UMC) Utrecht (Author)
  • Anthony J Miles - , University Medical Center (UMC) Utrecht (Author)
  • Diane Bouwmeester - , University Medical Center (UMC) Utrecht (Author)
  • Sander R van Hooff - , University Medical Center (UMC) Utrecht (Author)
  • Harm van Bakel - , University Medical Center (UMC) Utrecht (Author)
  • Erik Sluiters - , University Medical Center (UMC) Utrecht (Author)
  • Linda V Bakker - , University Medical Center (UMC) Utrecht (Author)
  • Berend Snel - , Utrecht University (Author)
  • Philip Lijnzaad - , University Medical Center (UMC) Utrecht (Author)
  • Dik van Leenen - , University Medical Center (UMC) Utrecht (Author)
  • Marian J A Groot Koerkamp - , University Medical Center (UMC) Utrecht (Author)
  • Frank C P Holstege - , University Medical Center (UMC) Utrecht (Author)

Abstract

To understand regulatory systems, it would be useful to uniformly determine how different components contribute to the expression of all other genes. We therefore monitored mRNA expression genome-wide, for individual deletions of one-quarter of yeast genes, focusing on (putative) regulators. The resulting genetic perturbation signatures reflect many different properties. These include the architecture of protein complexes and pathways, identification of expression changes compatible with viability, and the varying responsiveness to genetic perturbation. The data are assembled into a genetic perturbation network that shows different connectivities for different classes of regulators. Four feed-forward loop (FFL) types are overrepresented, including incoherent type 2 FFLs that likely represent feedback. Systematic transcription factor classification shows a surprisingly high abundance of gene-specific repressors, suggesting that yeast chromatin is not as generally restrictive to transcription as is often assumed. The data set is useful for studying individual genes and for discovering properties of an entire regulatory system.

Details

Original languageEnglish
Pages (from-to)740-752
Number of pages13
JournalCell
Volume157
Issue number3
Publication statusPublished - 24 Apr 2014
Peer-reviewedYes
Externally publishedYes

External IDs

Scopus 84899514789
ORCID /0000-0003-4306-930X/work/141545234

Keywords

Keywords

  • Gene Deletion, Gene Expression Regulation, Fungal, Gene Knockout Techniques, Gene Regulatory Networks, Genetic Techniques, Saccharomyces cerevisiae/genetics, Transcriptome

Library keywords