Control of yeast filamentous-form growth by modules in an integrated molecular network.
On solid growth media with limiting nitrogen source, diploid budding-yeast cells differentiate from the yeast form to a filamentous, adhesive, and invasive form. Genomic profiles of mRNA levels in Saccharomyces cerevisiae yeast-form and filamentous-form cells were compared. Disparate data types, including genes implicated by expression change, filamentation genes known previously through a phenotype, protein-protein interaction data, and protein-metabolite interaction data were integrated as the nodes and edges of a filamentation-network graph. Application of a network-clustering method revealed 47 clusters in the data. The correspondence of the clusters to modules is supported by significant coordinated expression change among cluster co-member genes, and the quantitative identification of collective functions controlling cell properties. The modular abstraction of the filamentation network enables the association of filamentous-form cell properties with the activation or repression of specific biological processes, and suggests hypotheses. A module-derived hypothesis was tested. It was found that the 26S proteasome regulates filamentous-form growth.
Institute for Systems Biology, Seattle, Washington 98103, USA.
Susanne
S
Prinz
Iliana
I
Avila-Campillo
Christine
C
Aldridge
Ajitha
A
Srinivasan
Krassen
K
Dimitrov
Andrew F
AF
Siegel
Timothy
T
Galitski
D002453:Cell Cycle / Q000235:genetics; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D005800:Genes, Fungal / Q000235:genetics / Q000502:physiology; D046988:Proteasome Endopeptidase Complex; D025941:Protein Interaction Mapping; D012331:RNA, Fungal / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology
C082719:CLN1 protein, S cerevisiae; D016213:Cyclins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; C074096:RPN12 protein, S cerevisiae; C119430:RPN4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex