Structure-system correlation identifies a gene regulatory Mediator submodule

Laurent Larivière; Martin Seizl; Sake Van Wageningen; Susanne Röther; Loes Van De Pasch; Heidi Feldmann; Katja Sträßer; Steve Hahn; Frank C.P. Holstege; Patrick Cramer

doi:10.1101/gad.465108

Structure-system correlation identifies a gene regulatory Mediator submodule

Laurent Larivière
, Martin Seizl
, Sake Van Wageningen
, Susanne Röther
, Loes Van De Pasch
, Heidi Feldmann
, Katja Sträßer
, Steve Hahn
, Frank C.P. Holstege
, Patrick Cramer

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

33 Citations (Scopus)

Abstract

A combination of crystallography, biochemistry, and gene expression analysis identifies the coactivator subcomplex Med8C/18/20 as a functionally distinct submodule of the Mediator head module. Med8C forms a conserved α-helix that tethers Med18/20 to the Mediator. Deletion of Med8C in vivo results in dissociation of Med18/20 from Mediator and in loss of transcription activity of extracts. Deletion of med8C, med18, or med20 causes similar changes in the yeast transcriptome, establishing Med8C/18/20 as a predominantly positive, genespecific submodule required for low transcription levels of nonactivated genes, including conjugation genes. The presented structure-based system perturbation is superior to gene deletion analysis of gene regulation.

Original language	English
Pages (from-to)	872-877
Number of pages	6
Journal	Genes and Development
Volume	22
Issue number	7
DOIs	https://doi.org/10.1101/gad.465108
Publication status	Published - 1 Apr 2008
Externally published	Yes

Keywords

Mediator of transcriptional regulation
Molecular systems biology
Multiprotein coactivator complex
RNA polymerase II transcription
Structure-function analysis

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10.1101/gad.465108

Cite this

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title = "Structure-system correlation identifies a gene regulatory Mediator submodule",

abstract = "A combination of crystallography, biochemistry, and gene expression analysis identifies the coactivator subcomplex Med8C/18/20 as a functionally distinct submodule of the Mediator head module. Med8C forms a conserved α-helix that tethers Med18/20 to the Mediator. Deletion of Med8C in vivo results in dissociation of Med18/20 from Mediator and in loss of transcription activity of extracts. Deletion of med8C, med18, or med20 causes similar changes in the yeast transcriptome, establishing Med8C/18/20 as a predominantly positive, genespecific submodule required for low transcription levels of nonactivated genes, including conjugation genes. The presented structure-based system perturbation is superior to gene deletion analysis of gene regulation.",

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doi = "10.1101/gad.465108",

language = "English",

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AU - Larivière, Laurent

AU - Seizl, Martin

AU - Van Wageningen, Sake

AU - Röther, Susanne

AU - Van De Pasch, Loes

AU - Feldmann, Heidi

AU - Sträßer, Katja

AU - Hahn, Steve

AU - Holstege, Frank C.P.

AU - Cramer, Patrick

PY - 2008/4/1

Y1 - 2008/4/1

N2 - A combination of crystallography, biochemistry, and gene expression analysis identifies the coactivator subcomplex Med8C/18/20 as a functionally distinct submodule of the Mediator head module. Med8C forms a conserved α-helix that tethers Med18/20 to the Mediator. Deletion of Med8C in vivo results in dissociation of Med18/20 from Mediator and in loss of transcription activity of extracts. Deletion of med8C, med18, or med20 causes similar changes in the yeast transcriptome, establishing Med8C/18/20 as a predominantly positive, genespecific submodule required for low transcription levels of nonactivated genes, including conjugation genes. The presented structure-based system perturbation is superior to gene deletion analysis of gene regulation.

AB - A combination of crystallography, biochemistry, and gene expression analysis identifies the coactivator subcomplex Med8C/18/20 as a functionally distinct submodule of the Mediator head module. Med8C forms a conserved α-helix that tethers Med18/20 to the Mediator. Deletion of Med8C in vivo results in dissociation of Med18/20 from Mediator and in loss of transcription activity of extracts. Deletion of med8C, med18, or med20 causes similar changes in the yeast transcriptome, establishing Med8C/18/20 as a predominantly positive, genespecific submodule required for low transcription levels of nonactivated genes, including conjugation genes. The presented structure-based system perturbation is superior to gene deletion analysis of gene regulation.

KW - Mediator of transcriptional regulation

KW - Molecular systems biology

KW - Multiprotein coactivator complex

KW - RNA polymerase II transcription

KW - Structure-function analysis

UR - https://www.scopus.com/pages/publications/41649112169

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DO - 10.1101/gad.465108

M3 - Article

C2 - 18381891

AN - SCOPUS:41649112169

SN - 0890-9369

VL - 22

SP - 872

EP - 877

JO - Genes and Development

JF - Genes and Development

IS - 7

ER -

Structure-system correlation identifies a gene regulatory Mediator submodule

Abstract

Keywords

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