m:Explorer: multinomial regression models reveal positive and negative regulators of longevity in yeast quiescence.
We developed m:Explorer for identifying process-specific transcription factors (TFs) from multiple genome-wide sources, including transcriptome, DNA-binding and chromatin data. m:Explorer robustly outperforms similar techniques in finding cell cycle TFs in Saccharomyces cerevisiae. We predicted and experimentally tested regulators of quiescence (G0), a model of ageing, over a six-week time-course. We validated nine of top-12 predictions as novel G0 TFs, including Δmga2, Δcst6, Δbas1 with higher viability and G0-essential TFs Tup1, Swi3. Pathway analysis associates longevity to reduced growth, reprogrammed metabolism and cell wall remodeling. m:Explorer (http://biit.cs.ut.ee/mexplorer/) is instrumental in interrogating eukaryotic regulatory systems using heterogeneous data.
EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK. juri.reimand@utoronto.ca
Jüri
J
Reimand
Anu
A
Aun
Jaak
J
Vilo
Juan M
JM
Vaquerizas
Juhan
J
Sedman
Nicholas M
NM
Luscombe
D000465:Algorithms; D001665:Binding Sites; D002453:Cell Cycle; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D020407:Internet; D016015:Logistic Models; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D050296:Microbial Viability / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C542266:MGA2 protein, S cerevisiae; D008565:Membrane Proteins; D009687:Nuclear Proteins; D009707:Nucleosomes; D012097:Repressor Proteins; C072981:SWI3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C066502:TUP1 protein, S cerevisiae; D014157:Transcription Factors