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

P.P.C.W. Kemmeren; K. Sameith; L.A.L. van de Pasch; J.J. Benschop; T.L. Lenstra; A. Margaritis; E. O'Duibhir; E. Apweiler; S. van Wageningen; C.W. Ko; S.A.A.C. van Heesch; M.M. Kashani; G. Ampatziadis-Michailidis; M.O. Brok; N.A.C.H. Brabers; A.J. Miles; D. Bouwmeester; S.R. van Hooff; H.H.M.J. van Bakel; E.C. Sluiters; L.V. Bakker; B. Snel; P. Lijnzaad; D. van Leenen; M.J.A. Groot Koerkamp; F.C.P. Holstege

doi:10.1016/j.cell.2014.02.054

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

P.P.C.W. Kemmeren, K. Sameith, L.A.L. van de Pasch, J.J. Benschop, T.L. Lenstra, A. Margaritis, E. O'Duibhir, E. Apweiler, S. van Wageningen, C.W. Ko, S.A.A.C. van Heesch, M.M. Kashani, G. Ampatziadis-Michailidis, M.O. Brok, N.A.C.H. Brabers, A.J. Miles, D. Bouwmeester, S.R. van Hooff, H.H.M.J. van Bakel, E.C. SluitersL.V. Bakker, B. Snel, P. Lijnzaad, D. van Leenen, M.J.A. Groot Koerkamp, F.C.P. Holstege

Research output: Contribution to journal › Article › Academic › peer-review

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 genomewide,
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.

Original language	Undefined/Unknown
Pages (from-to)	740-752
Number of pages	13
Journal	Cell
Volume	157
DOIs	https://doi.org/10.1016/j.cell.2014.02.054
Publication status	Published - 2014

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Kemmeren, P. P. C. W., Sameith, K., van de Pasch, L. A. L., Benschop, J. J., Lenstra, T. L., Margaritis, A., O'Duibhir, E., Apweiler, E., van Wageningen, S., Ko, C. W., van Heesch, S. A. A. C., Kashani, M. M., Ampatziadis-Michailidis, G., Brok, M. O., Brabers, N. A. C. H., Miles, A. J., Bouwmeester, D., van Hooff, S. R., van Bakel, H. H. M. J., ... Holstege, F. C. P. (2014). Large-scale genetic perturbations reveal regulatory networks and an abundance of gene-specific repressors. Cell, 157, 740-752. https://doi.org/10.1016/j.cell.2014.02.054

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title = "Large-scale genetic perturbations reveal regulatory networks and an abundance of gene-specific repressors",

abstract = "To understand regulatory systems, it would be usefulto uniformly determine how different componentscontribute to the expression of all other genes. Wetherefore monitored mRNA expression genomewide,for individual deletions of one-quarter of yeastgenes, focusing on (putative) regulators. The resultinggenetic perturbation signatures reflect manydifferent properties. These include the architectureof protein complexes and pathways, identificationof expression changes compatible with viability,and the varying responsiveness to genetic perturbation.The data are assembled into a genetic perturbationnetwork that shows different connectivities fordifferent classes of regulators. Four feed-forwardloop (FFL) types are overrepresented, including incoherenttype 2 FFLs that likely represent feedback.Systematic transcription factor classification showsa surprisingly high abundance of gene-specific repressors,suggesting that yeast chromatin is not asgenerally restrictive to transcription as is oftenassumed. The data set is useful for studying individualgenes and for discovering properties of an entireregulatory system.",

author = "P.P.C.W. Kemmeren and K. Sameith and {van de Pasch}, L.A.L. and J.J. Benschop and T.L. Lenstra and A. Margaritis and E. O'Duibhir and E. Apweiler and {van Wageningen}, S. and C.W. Ko and {van Heesch}, S.A.A.C. and M.M. Kashani and G. Ampatziadis-Michailidis and M.O. Brok and N.A.C.H. Brabers and A.J. Miles and D. Bouwmeester and {van Hooff}, S.R. and {van Bakel}, H.H.M.J. and E.C. Sluiters and L.V. Bakker and B. Snel and P. Lijnzaad and {van Leenen}, D. and {Groot Koerkamp}, M.J.A. and F.C.P. Holstege",

year = "2014",

doi = "10.1016/j.cell.2014.02.054",

language = "Undefined/Unknown",

volume = "157",

pages = "740--752",

journal = "Cell",

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Kemmeren, PPCW, Sameith, K, van de Pasch, LAL, Benschop, JJ, Lenstra, TL, Margaritis, A, O'Duibhir, E, Apweiler, E, van Wageningen, S, Ko, CW, van Heesch, SAAC, Kashani, MM, Ampatziadis-Michailidis, G, Brok, MO, Brabers, NACH, Miles, AJ, Bouwmeester, D, van Hooff, SR, van Bakel, HHMJ, Sluiters, EC, Bakker, LV, Snel, B, Lijnzaad, P, van Leenen, D, Groot Koerkamp, MJA & Holstege, FCP 2014, 'Large-scale genetic perturbations reveal regulatory networks and an abundance of gene-specific repressors', Cell, vol. 157, pp. 740-752. https://doi.org/10.1016/j.cell.2014.02.054

TY - JOUR

T1 - Large-scale genetic perturbations reveal regulatory networks and an abundance of gene-specific repressors

AU - Kemmeren, P.P.C.W.

AU - Sameith, K.

AU - van de Pasch, L.A.L.

AU - Benschop, J.J.

AU - Lenstra, T.L.

AU - Margaritis, A.

AU - O'Duibhir, E.

AU - Apweiler, E.

AU - van Wageningen, S.

AU - Ko, C.W.

AU - van Heesch, S.A.A.C.

AU - Kashani, M.M.

AU - Ampatziadis-Michailidis, G.

AU - Brok, M.O.

AU - Brabers, N.A.C.H.

AU - Miles, A.J.

AU - Bouwmeester, D.

AU - van Hooff, S.R.

AU - van Bakel, H.H.M.J.

AU - Sluiters, E.C.

AU - Bakker, L.V.

AU - Snel, B.

AU - Lijnzaad, P.

AU - van Leenen, D.

AU - Groot Koerkamp, M.J.A.

AU - Holstege, F.C.P.

PY - 2014

Y1 - 2014

N2 - To understand regulatory systems, it would be usefulto uniformly determine how different componentscontribute to the expression of all other genes. Wetherefore monitored mRNA expression genomewide,for individual deletions of one-quarter of yeastgenes, focusing on (putative) regulators. The resultinggenetic perturbation signatures reflect manydifferent properties. These include the architectureof protein complexes and pathways, identificationof expression changes compatible with viability,and the varying responsiveness to genetic perturbation.The data are assembled into a genetic perturbationnetwork that shows different connectivities fordifferent classes of regulators. Four feed-forwardloop (FFL) types are overrepresented, including incoherenttype 2 FFLs that likely represent feedback.Systematic transcription factor classification showsa surprisingly high abundance of gene-specific repressors,suggesting that yeast chromatin is not asgenerally restrictive to transcription as is oftenassumed. The data set is useful for studying individualgenes and for discovering properties of an entireregulatory system.

AB - To understand regulatory systems, it would be usefulto uniformly determine how different componentscontribute to the expression of all other genes. Wetherefore monitored mRNA expression genomewide,for individual deletions of one-quarter of yeastgenes, focusing on (putative) regulators. The resultinggenetic perturbation signatures reflect manydifferent properties. These include the architectureof protein complexes and pathways, identificationof expression changes compatible with viability,and the varying responsiveness to genetic perturbation.The data are assembled into a genetic perturbationnetwork that shows different connectivities fordifferent classes of regulators. Four feed-forwardloop (FFL) types are overrepresented, including incoherenttype 2 FFLs that likely represent feedback.Systematic transcription factor classification showsa surprisingly high abundance of gene-specific repressors,suggesting that yeast chromatin is not asgenerally restrictive to transcription as is oftenassumed. The data set is useful for studying individualgenes and for discovering properties of an entireregulatory system.

U2 - 10.1016/j.cell.2014.02.054

DO - 10.1016/j.cell.2014.02.054

M3 - Article

SN - 0092-8674

VL - 157

SP - 740

EP - 752

JO - Cell

JF - Cell

ER -