Transcriptional Regulatory Networks in Saccharomyces cerevisiae

We have determined how most of the transcriptional regulators encoded in the eukaryote Saccharomyces cerevisiaeassociate with genes across the genome in living cells. Just as maps of metabolic networks describe the potential pathways that may be used by a cell to accomplish metabolic processes, this network of regulator-gene interactions describes potential pathways yeast cells can use to regulate global gene expression programs. We use this information to identify network motifs, the simplest units of network architecture, and demonstrate that an automated process can use motifs to assemble a transcriptional regulatory network structure. Our results reveal that eukaryotic cellular functions are highly connected through networks of transcriptional regulators that regulate other transcriptional regulators.

[1]  D. Koshland,et al.  Ultrasensitivity in biochemical systems controlled by covalent modification. Interplay between zero-order and multistep effects. , 1984, The Journal of biological chemistry.

[2]  S. Fields,et al.  Overproduction of the yeast STE12 protein leads to constitutive transcriptional induction. , 1990, Genes & development.

[3]  Regulation of thiamine biosynthesis in Saccharomyces cerevisiae , 1990, Journal of bacteriology.

[4]  Y. Kaneko,et al.  Cloning and characteristics of a positive regulatory gene, THI2 (PHO6), of thiamin biosynthesis in Saccharomyces cerevisiae , 1992, FEBS letters.

[5]  AC Tose.  Cell , 1993, Cell.

[6]  Thomas Lengauer,et al.  Proceedings of the Seventh International Conference on Intelligent Systems for Molecular Biology , 1998, ISMB 1999.

[7]  P. Thuriaux,et al.  Suppression of yeast RNA polymerase III mutations by FHL1, a gene coding for a fork head protein involved in rRNA processing , 1994, Molecular and cellular biology.

[8]  L. Johnston,et al.  A yeast transcription factor bypassing the requirement for SBF and DSC1/MBF in budding yeast has homology to bacterial signal transduction proteins. , 1995, The EMBO journal.

[9]  P. Brown,et al.  Exploring the metabolic and genetic control of gene expression on a genomic scale. , 1997, Science.

[10]  A. Arkin,et al.  Stochastic mechanisms in gene expression. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Araceli M. Huerta,et al.  From specific gene regulation to genomic networks: a global analysis of transcriptional regulation in Escherichia coli. , 1998, BioEssays : news and reviews in molecular, cellular and developmental biology.

[12]  D. Botstein,et al.  The transcriptional program of sporulation in budding yeast. , 1998, Science.

[13]  Ronald W. Davis,et al.  A genome-wide transcriptional analysis of the mitotic cell cycle. , 1998, Molecular cell.

[14]  Michael Ruogu Zhang,et al.  Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. , 1998, Molecular biology of the cell.

[15]  K. Siegers,et al.  Epitope tagging of yeast genes using a PCR‐based strategy: more tags and improved practical routines , 1999, Yeast.

[16]  Michael Costanzo,et al.  Regulation of Transcription at theSaccharomyces cerevisiae Start Transition by Stb1, a Swi6-Binding Protein , 1999, Molecular and Cellular Biology.

[17]  L. Johnston,et al.  Association of the cell cycle transcription factor Mbp1 with the Skn7 response regulator in budding yeast. , 1999, Molecular biology of the cell.

[18]  L. Samson,et al.  Global response of Saccharomyces cerevisiae to an alkylating agent. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[19]  E. Lander,et al.  Effectors of a developmental mitogen-activated protein kinase cascade revealed by expression signatures of signaling mutants. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. Tjian,et al.  Orchestrated response: a symphony of transcription factors for gene control. , 2000, Genes & development.

[21]  T. Hughes,et al.  Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles. , 2000, Science.

[22]  Yudong D. He,et al.  Functional Discovery via a Compendium of Expression Profiles , 2000, Cell.

[23]  Peter Walter,et al.  Functional and Genomic Analyses Reveal an Essential Coordination between the Unfolded Protein Response and ER-Associated Degradation , 2000, Cell.

[24]  D. Botstein,et al.  Genome-wide characterization of the Zap1p zinc-responsive regulon in yeast. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[25]  R. Young,et al.  Transcription of eukaryotic protein-coding genes. , 2000, Annual review of genetics.

[26]  Michael E. Cusick,et al.  The Yeast Proteome Database (YPD) and Caenorhabditis elegans Proteome Database (WormPD): comprehensive resources for the organization and comparison of model organism protein information , 2000, Nucleic Acids Res..

[27]  D. Botstein,et al.  Genomic expression programs in the response of yeast cells to environmental changes. , 2000, Molecular biology of the cell.

[28]  L. Serrano,et al.  Engineering stability in gene networks by autoregulation , 2000, Nature.

[29]  Stuart L. Schreiber,et al.  Partitioning the transcriptional program induced by rapamycin among the effectors of the Tor proteins , 2000, Current Biology.

[30]  Henry V. Baker,et al.  Understanding the Growth Phenotype of the Yeastgcr1 Mutant in Terms of Global Genomic Expression Patterns , 2000, Journal of bacteriology.

[31]  John J. Wyrick,et al.  Genome-Wide Distribution of ORC and MCM Proteins in S. cerevisiae: High-Resolution Mapping of Replication Origins , 2001, Science.

[32]  E. Lander,et al.  Remodeling of yeast genome expression in response to environmental changes. , 2001, Molecular biology of the cell.

[33]  Nicola J. Rinaldi,et al.  Serial Regulation of Transcriptional Regulators in the Yeast Cell Cycle , 2001, Cell.

[34]  C. Garvie,et al.  Recognition of specific DNA sequences. , 2001, Molecular cell.

[35]  D. Botstein,et al.  Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF , 2001, Nature.

[36]  Varshal K. Davé,et al.  Genome-wide responses to mitochondrial dysfunction. , 2001, Molecular biology of the cell.

[37]  M. Ptashne,et al.  Genes and Signals , 2001 .

[38]  David Botstein,et al.  Promoter-specific binding of Rap1 revealed by genome-wide maps of protein–DNA association , 2001, Nature Genetics.

[39]  M. Marton,et al.  Transcriptional Profiling Shows that Gcn4p Is a Master Regulator of Gene Expression during Amino Acid Starvation in Yeast , 2001, Molecular and Cellular Biology.

[40]  C. Jacq,et al.  Genome‐wide studies on the nuclear PDR3‐controlled response to mitochondrial dysfunction in yeast , 2002, FEBS letters.

[41]  P. Bourgine,et al.  Topological and causal structure of the yeast transcriptional regulatory network , 2002, Nature Genetics.

[42]  S. Shen-Orr,et al.  Network motifs in the transcriptional regulation network of Escherichia coli , 2002, Nature Genetics.

[43]  J. Ferrell.  Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. , 2002, Current opinion in cell biology.

[44]  G. Orphanides,et al.  A Unified Theory of Gene Expression , 2002, Cell.