m:Explorer: multinomial regression models reveal positive and negative regulators of longevity in yeast quiescence

Genome Biol. 2012 Jun 21;13(6):R55. doi: 10.1186/gb-2012-13-6-r55.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Algorithms*
  • Binding Sites
  • Cell Cycle
  • Cell Wall / genetics
  • Cell Wall / metabolism
  • Computational Biology / methods
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Internet
  • Logistic Models*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microbial Viability / genetics*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • MGA2 protein, S cerevisiae
  • Membrane Proteins
  • Nuclear Proteins
  • Nucleosomes
  • Repressor Proteins
  • SWI3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • TUP1 protein, S cerevisiae
  • Transcription Factors