Abstract：
:We have developed a highly parallel strategy, systematic gene-to-phenotype arrays (SGPAs), to comprehensively map the genetic landscape driving molecular phenotypes of interest. By this approach, a complete yeast genetic mutant array is crossed with fluorescent reporters and imaged on membranes at high density and contrast. Importantly, SGPA enables quantification of phenotypes that are not readily detectable in ordinary genetic analysis of cell fitness. We benchmark SGPA by examining two fundamental biological phenotypes: first, we explore glucose repression, in which SGPA identifies a requirement for the Mediator complex and a role for the CDK8/kinase module in regulating transcription. Second, we examine selective protein quality control, in which SGPA identifies most known quality control factors along with U34 tRNA modification, which acts independently of proteasomal degradation to limit misfolded protein production. Integration of SGPA with other fluorescent readouts will enable genetic dissection of a wide range of biological pathways and conditions.
journal_name
Mol Celljournal_title
Molecular cellauthors
Jaeger PA,Ornelas L,McElfresh C,Wong LR,Hampton RY,Ideker Tdoi
10.1016/j.molcel.2017.12.016subject
Has Abstractpub_date
2018-01-18 00:00:00pages
321-333.e3issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(17)30968-1journal_volume
69pub_type
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