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
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Research Support, Non-U.S. Gov't
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Validation Study
MeSH terms
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Algorithms*
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Binding Sites
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Cell Cycle
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Cell Wall / genetics
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Cell Wall / metabolism
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Computational Biology / methods
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Gene Expression Regulation, Fungal
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Genes, Fungal
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Internet
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Logistic Models*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Microbial Viability / genetics*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Nucleosomes / genetics
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Nucleosomes / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Time Factors
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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MGA2 protein, S cerevisiae
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Membrane Proteins
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Nuclear Proteins
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Nucleosomes
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Repressor Proteins
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SWI3 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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TUP1 protein, S cerevisiae
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Transcription Factors