Large-scale genetic perturbations reveal regulatory networks and an abundance of gene-specific repressors.
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.
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Patrick
P
Kemmeren
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Katrin
K
Sameith
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Loes A L
LA
van de Pasch
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Joris J
JJ
Benschop
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Tineke L
TL
Lenstra
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Thanasis
T
Margaritis
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Eoghan
E
O'Duibhir
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Eva
E
Apweiler
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Sake
S
van Wageningen
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Cheuk W
CW
Ko
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Sebastiaan
S
van Heesch
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Mehdi M
MM
Kashani
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Giannis
G
Ampatziadis-Michailidis
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Mariel O
MO
Brok
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Nathalie A C H
NA
Brabers
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Anthony J
AJ
Miles
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Diane
D
Bouwmeester
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Sander R
SR
van Hooff
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Harm
H
van Bakel
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Erik
E
Sluiters
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Linda V
LV
Bakker
Theoretical Biology and Bioinformatics, Department of Biology, Utrecht University, Utrecht 3584 CG, the Netherlands.
Berend
B
Snel
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Philip
P
Lijnzaad
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Dik
D
van Leenen
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands.
Marian J A
MJ
Groot Koerkamp
Molecular Cancer Research, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht 3584 CG, the Netherlands. Electronic address: f.c.p.holstege@umcutrecht.nl.
Frank C P
FC
Holstege
D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D053263:Gene Regulatory Networks; D005821:Genetic Techniques; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D059467:Transcriptome