TY - JOUR
T1 - Structure-system correlation identifies a gene regulatory Mediator submodule
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 - http://www.scopus.com/inward/record.url?scp=41649112169&partnerID=8YFLogxK
U2 - 10.1101/gad.465108
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 -