Inferring transcriptional modules from ChIP-chip, motif and microarray data

Abstract'ReMoDiscovery' is an intuitive algorithm to correlate regulatory programs with regulators and corresponding motifs to a set of co-expressed genes. It exploits in a concurrent way three independent data sources: ChIP-chip data, motif information and gene expression profiles. When compared to published module discovery algorithms, ReMoDiscovery is fast and easily tunable. We evaluated our method on yeast data, where it was shown to generate biologically meaningful findings and allowed the prediction of potential novel roles of transcriptional regulators.

[1]  E. Herrero,et al.  RCS1, a gene involved in controlling cell size in Saccharomyces cerevisiae , 1991, Yeast.

[2]  L. Guarente,et al.  Regulation of the yeast CYT1 gene encoding cytochrome c1 by HAP1 and HAP2/3/4. , 1991, Molecular and cellular biology.

[3]  C. Devlin,et al.  RAP1 is required for BAS1/BAS2- and GCN4-dependent transcription of the yeast HIS4 gene , 1991, Molecular and cellular biology.

[4]  C. Lowry,et al.  Regulation of gene expression by oxygen in Saccharomyces cerevisiae. , 1992, Microbiological reviews.

[5]  K. Nasmyth,et al.  A role for the transcription factors Mbp1 and Swi4 in progression from G1 to S phase. , 1993, Science.

[6]  Tomasz Imielinski,et al.  Mining association rules between sets of items in large databases , 1993, SIGMOD Conference.

[7]  T. Cooper,et al.  Regulatory circuit for responses of nitrogen catabolic gene expression to the GLN3 and DAL80 proteins and nitrogen catabolite repression in Saccharomyces cerevisiae , 1993, Journal of bacteriology.

[8]  A. Mitchell Control of meiotic gene expression in Saccharomyces cerevisiae. , 1994, Microbiological reviews.

[9]  D. Thiele,et al.  Identification and analysis of a Saccharomyces cerevisiae copper homeostasis gene encoding a homeodomain protein , 1994, Molecular and cellular biology.

[10]  K. Struhl,et al.  Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity , 1994, Molecular and Cellular Biology.

[11]  J. Deckert,et al.  Multiple elements and auto-repression regulate Rox1, a repressor of hypoxic genes in Saccharomyces cerevisiae. , 1995, Genetics.

[12]  T. Cooper,et al.  The Saccharomyces cerevisiae Leu3 protein activates expression of GDH1, a key gene in nitrogen assimilation , 1995, Molecular and cellular biology.

[13]  R. E. Esposito,et al.  UME6 is a central component of a developmental regulatory switch controlling meiosis-specific gene expression. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[14]  A. Schmitt,et al.  Msn2p, a zinc finger DNA-binding protein, is the transcriptional activator of the multistress response in Saccharomyces cerevisiae. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  A. Marchler-Bauer,et al.  The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE). , 1996, The EMBO journal.

[16]  L. Breeden,et al.  Xbp1, a stress-induced transcriptional repressor of the Saccharomyces cerevisiae Swi4/Mbp1 family , 1997, Molecular and cellular biology.

[17]  P. Blaiseau,et al.  Met31p and Met32p, two related zinc finger proteins, are involved in transcriptional regulation of yeast sulfur amino acid metabolism , 1997, Molecular and cellular biology.

[18]  Metabolism of sulfur amino acids in Saccharomyces cerevisiae. , 1997, Microbiology and molecular biology reviews : MMBR.

[19]  M. Spector,et al.  Hir1p and Hir2p function as transcriptional corepressors to regulate histone gene transcription in the Saccharomyces cerevisiae cell cycle , 1997, Molecular and cellular biology.

[20]  B Hamilton,et al.  Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity. , 1998, Genes & development.

[21]  P. Blaiseau,et al.  Multiple transcriptional activation complexes tether the yeast activator Met4 to DNA , 1998, The EMBO journal.

[22]  G. Braus,et al.  Monitoring the Gcn4 Protein-mediated Response in the YeastSaccharomyces cerevisiae * , 1998, The Journal of Biological Chemistry.

[23]  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.

[24]  P. Briza,et al.  Sporulation-specific expression of the yeast DIT1/DIT2 promoter is controlled by a newly identified repressor element and the short form of Rim101p. , 1998, European journal of biochemistry.

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

[26]  T. Powers,et al.  Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae. , 1999, Molecular biology of the cell.

[27]  David Lydall,et al.  NDD1, a High-Dosage Suppressor ofcdc28-1N, Is Essential for Expression of a Subset of Late-S-Phase-Specific Genes in Saccharomyces cerevisiae , 1999, Molecular and Cellular Biology.

[28]  Jacob Hofman-Bang,et al.  Nitrogen catabolite repression in Saccharomyces cerevisiae , 1999, Molecular biotechnology.

[29]  Youyong Zhu,et al.  Genetic diversity and disease control in rice , 2000, Nature.

[30]  D. Raitt,et al.  The Skn7 response regulator of Saccharomyces cerevisiae interacts with Hsf1 in vivo and is required for the induction of heat shock genes by oxidative stress. , 2000, Molecular biology of the cell.

[31]  D. Botstein,et al.  Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth , 2000, Nature.

[32]  B. Daignan-Fornier,et al.  Redox regulation of AMP synthesis in yeast: a role of the Bas1p and Bas2p transcription factors , 2000, Molecular microbiology.

[33]  J. D. de Winde,et al.  Nutrient-induced signal transduction through the protein kinase A pathway and its role in the control of metabolism, stress resistance, and growth in yeast. , 2000, Enzyme and microbial technology.

[34]  Joseph Heitman,et al.  Sok2 Regulates Yeast Pseudohyphal Differentiation via a Transcription Factor Cascade That Regulates Cell-Cell Adhesion , 2000, Molecular and Cellular Biology.

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

[36]  A. Shevchenko,et al.  Forkhead transcription factors, Fkh1p and Fkh2p, collaborate with Mcm1p to control transcription required for M-phase , 2000, Current Biology.

[37]  Cristina Aranda,et al.  TOR Modulates GCN4-Dependent Expression of Genes Turned on by Nitrogen Limitation , 2001, Journal of bacteriology.

[38]  Fred Winston,et al.  NRG1 is required for glucose repression of the SUC2 and GAL genes of Saccharomyces cerevisiae , 2001, BMC Genetics.

[39]  J. Gancedo Control of pseudohyphae formation in Saccharomyces cerevisiae. , 2001, FEMS microbiology reviews.

[40]  Galit Shenhar,et al.  A Positive Regulator of Mitosis, Sok2, Functions as a Negative Regulator of Meiosis in Saccharomyces cerevisiae , 2001, Molecular and Cellular Biology.

[41]  B. Moudni,et al.  Sut1p interaction with Cyc8p(Ssn6p) relieves hypoxic genes from Cyc8p–Tup1p repression in Saccharomyces cerevisiae , 2001, Molecular microbiology.

[42]  M. Gerstein,et al.  Interrelating different types of genomic data, from proteome to secretome: 'oming in on function. , 2001, Genome research.

[43]  Francesc Posas,et al.  Multiple Levels of Control Regulate the Yeast cAMP-response Element-binding Protein Repressor Sko1p in Response to Stress* , 2001, The Journal of Biological Chemistry.

[44]  D. Stillman,et al.  The Swi5 activator recruits the Mediator complex to the HO promoter without RNA polymerase II. , 2001, Genes & development.

[45]  J. Heitman,et al.  The TOR signal transduction cascade controls cellular differentiation in response to nutrients. , 2001, Molecular biology of the cell.

[46]  T. Furuchi,et al.  Two nuclear proteins, Cin5 and Ydr259c, confer resistance to cisplatin in Saccharomyces cerevisiae. , 2001, Molecular pharmacology.

[47]  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.

[48]  Stefan Hohmann,et al.  Yeast Stress Responses , 1997, Topics in Current Genetics.

[49]  T. Cooper Transmitting the signal of excess nitrogen in Saccharomyces cerevisiae from the Tor proteins to the GATA factors: connecting the dots. , 2002, FEMS microbiology reviews.

[50]  D. Timson,et al.  Gal3p and Gal1p interact with the transcriptional repressor Gal80p to form a complex of 1:1 stoichiometry. , 2002, The Biochemical journal.

[51]  Nicola J. Rinaldi,et al.  Transcriptional Regulatory Networks in Saccharomyces cerevisiae , 2002, Science.

[52]  I. S. Pretorius,et al.  The sensing of nutritional status and the relationship to filamentous growth in Saccharomyces cerevisiae. , 2002, FEMS yeast research.

[53]  Valmik K. Vyas,et al.  Snf1 Protein Kinase and the Repressors Nrg1 and Nrg2 Regulate FLO11, Haploid Invasive Growth, and Diploid Pseudohyphal Differentiation , 2002, Molecular and Cellular Biology.

[54]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[55]  G. Kohlhaw Leucine Biosynthesis in Fungi: Entering Metabolism through the Back Door , 2003, Microbiology and Molecular Biology Reviews.

[56]  B. De Moor,et al.  In silico identification and experimental validation of PmrAB targets in Salmonella typhimurium by regulatory motif detection , 2004, Genome Biology.

[57]  M. J. Mallory,et al.  Ume1p Represses Meiotic Gene Transcription in Saccharomyces cerevisiae through Interaction with the Histone Deacetylase Rpd3p* , 2003, Journal of Biological Chemistry.

[58]  Hans-Joachim Schüller,et al.  Transcriptional control of nonfermentative metabolism in the yeast Saccharomyces cerevisiae , 2003, Current Genetics.

[59]  J. Winderickx,et al.  From feast to famine; adaptation to nutrient availability in yeast , 2003 .

[60]  Nicola J. Rinaldi,et al.  Computational discovery of gene modules and regulatory networks , 2003, Nature Biotechnology.

[61]  Michael Costanzo,et al.  G1 Transcription Factors Are Differentially Regulated in Saccharomyces cerevisiae by the Swi6-Binding Protein Stb1 , 2003, Molecular and Cellular Biology.

[62]  Yuan Zhou,et al.  Transcriptional regulation of yeast peroxiredoxin gene TSA2 through Hap1p, Rox1p, and Hap2/3/5p. , 2003, Free radical biology & medicine.

[63]  D. Pe’er,et al.  Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data , 2003, Nature Genetics.

[64]  C. V. Van Slyke,et al.  The essential transcription factor Reb1p interacts with the CLB2 UAS outside of the G2/M control region. , 2003, Nucleic acids research.

[65]  B. Birren,et al.  Sequencing and comparison of yeast species to identify genes and regulatory elements , 2003, Nature.

[66]  Dmitrij Frishman,et al.  MIPS: analysis and annotation of proteins from whole genomes in 2005 , 2005, Nucleic Acids Res..

[67]  Xiaojiang Xu,et al.  Learning module networks from genome‐wide location and expression data , 2004, FEBS letters.

[68]  M. Cosma Daughter‐specific repression of Saccharomyces cerevisiae HO: Ash1 is the commander , 2004, EMBO reports.

[69]  Michael Q. Zhang,et al.  Identifying combinatorial regulation of transcription factors and binding motifs , 2004, Genome Biology.

[70]  Roded Sharan,et al.  Revealing modularity and organization in the yeast molecular network by integrated analysis of highly heterogeneous genomewide data. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[71]  Joseph Mellor,et al.  Comparisons of predicted genetic modules: identification of co-expressed genes through module gene flow. , 2004, Genome informatics. International Conference on Genome Informatics.

[72]  C. Rodrigues-Pousada,et al.  YAP4 gene expression is induced in response to several forms of stress in Saccharomyces cerevisiae , 2004, Yeast.

[73]  Nicola J. Rinaldi,et al.  Transcriptional regulatory code of a eukaryotic genome , 2004, Nature.

[74]  T. Powers,et al.  Tor Signaling and Nutrient-based Signals Converge on Mks1p Phosphorylation to Regulate Expression of Rtg1p·Rtg3p-dependent Target Genes* , 2004, Journal of Biological Chemistry.

[75]  M. Hall,et al.  TOR Regulates Ribosomal Protein Gene Expression via PKA and the Forkhead Transcription Factor FHL1 , 2004, Cell.

[76]  D. Koller,et al.  Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[77]  M. Tyers,et al.  A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size. , 2004, Genes & development.

[78]  J. Gancedo,et al.  Pseudohyphal growth is induced in Saccharomyces cerevisiae by a combination of stress and cAMP signalling , 2000, Antonie van Leeuwenhoek.

[79]  Valmik K. Vyas,et al.  Repressors Nrg1 and Nrg2 Regulate a Set of Stress-Responsive Genes in Saccharomyces cerevisiae , 2005, Eukaryotic Cell.

[80]  D. Cavalieri,et al.  Bioinformatic methods for integrating whole-genome expression results into cellular networks. , 2005, Drug discovery today.

[81]  Michael P Washburn,et al.  The HIR corepressor complex binds to nucleosomes generating a distinct protein/DNA complex resistant to remodeling by SWI/SNF. , 2005, Genes & development.

[82]  M. Bewley,et al.  Gal80 Dimerization and the Yeast GAL Gene Switch , 2005, Genetics.

[83]  Kara Dolinski,et al.  Fungal BLAST and Model Organism BLASTP Best Hits: new comparison resources at the Saccharomyces Genome Database (SGD) , 2004, Nucleic Acids Res..

[84]  Hyunsoo Kim,et al.  Unraveling condition specific gene transcriptional regulatory networks in Saccharomyces cerevisiae , 2006, BMC Bioinformatics.

[85]  Curt Wittenberg,et al.  Cell cycle-dependent transcription in yeast: promoters, transcription factors, and transcriptomes , 2005, Oncogene.

[86]  B. Andrews,et al.  Reverse recruitment: the Nup84 nuclear pore subcomplex mediates Rap1/Gcr1/Gcr2 transcriptional activation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[87]  A. Hinnebusch Translational regulation of GCN4 and the general amino acid control of yeast. , 2005, Annual review of microbiology.

[88]  H. Friesen,et al.  Components of the ESCRT Pathway, DFG16, and YGR122w Are Required for Rim101 To Act as a Corepressor with Nrg1 at the Negative Regulatory Element of the DIT1 Gene of Saccharomyces cerevisiae , 2005, Molecular and Cellular Biology.

[89]  Lilia Alberghina,et al.  SFP1 is involved in cell size modulation in respiro‐fermentative growth conditions , 2005, Yeast.

[90]  L. Breeden,et al.  Identification of target genes of a yeast transcriptional repressor. , 2006, Methods in molecular biology.

[91]  Kathleen Marchal,et al.  Inferring Transcriptional Networks by Mining 'Omics' Data , 2006 .

[92]  M. Bewley,et al.  Intragenic Suppression of Gal3C Interaction With Gal80 in the Saccharomyces cerevisiae GAL Gene Switch , 2006, Genetics.