title: Growth-rate regulated genes have profound impact on interpretation of transcriptome profiling in Saccharomyces cerevisiae.
abstract: BACKGROUND
  Growth rate is central to the development of cells in all organisms. However, little is known about the impact of changing growth rates. We used continuous cultures to control growth rate and studied the transcriptional program of the model eukaryote Saccharomyces cerevisiae, with generation times varying between 2 and 35 hours.
  
  
  RESULTS
  A total of 5930 transcripts were identified at the different growth rates studied. Consensus clustering of these revealed that half of all yeast genes are affected by the specific growth rate, and that the changes are similar to those found when cells are exposed to different types of stress (>80% overlap). Genes with decreased transcript levels in response to faster growth are largely of unknown function (>50%) whereas genes with increased transcript levels are involved in macromolecular biosynthesis such as those that encode ribosomal proteins. This group also covers most targets of the transcriptional activator RAP1, which is also known to be involved in replication. A positive correlation between the location of replication origins and the location of growth-regulated genes suggests a role for replication in growth rate regulation.
  
  
  CONCLUSIONS
  Our data show that the cellular growth rate has great influence on transcriptional regulation. This, in turn, implies that one should be cautious when comparing mutants with different growth rates. Our findings also indicate that much of the regulation is coordinated via the chromosomal location of the affected genes, which may be valuable information for the control of heterologous gene expression in metabolic engineering.
authors.affiliation: Institut für Molekulare Biowissenschaften, Johann Wolfgang Goethe-Universität, Max-von-Laue-Str, 9, 60438 Frankfurt am Main, Germany. regenberg@em.uni-frankfurt.de
authors.forename: Birgitte
authors.initials: B
authors.lastname: Regenberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Grotkjaer
authors.forename: Ole
authors.initials: O
authors.lastname: Winther
authors.forename: Anders
authors.initials: A
authors.lastname: Fausbøll
authors.forename: Mats
authors.initials: M
authors.lastname: Akesson
authors.forename: Christoffer
authors.initials: C
authors.lastname: Bro
authors.forename: Lars Kai
authors.initials: LK
authors.lastname: Hansen
authors.forename: Søren
authors.initials: S
authors.lastname: Brunak
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D048708:Cell Growth Processes; D015825:Chromosomes, Fungal / Q000235:genetics; D016000:Cluster Analysis; D016384:Consensus Sequence; D000431:Ethanol / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D005800:Genes, Fungal / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018741:Replication Origin / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000254:growth & development*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D000431:Ethanol