Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 290 (5500): 2306-2309

Copyright © 2000 by the American Association for the Advancement of Science

Genome-Wide Location and Function of DNA Binding Proteins

Bing Ren,1* François Robert,1* John J. Wyrick,12* Oscar Aparicio,24 Ezra G. Jennings,12 Itamar Simon,1 Julia Zeitlinger,1 Jörg Schreiber,1 Nancy Hannett,1 Elenita Kanin,1 Thomas L. Volkert,1 Christopher J. Wilson,5 Stephen P. Bell,23 Richard A. Young12dagger

Understanding how DNA binding proteins control global gene expression and chromosomal maintenance requires knowledge of the chromosomal locations at which these proteins function in vivo. We developed a microarray method that reveals the genome-wide location of DNA-bound proteins and used this method to monitor binding of gene-specific transcription activators in yeast. A combination of location and expression profiles was used to identify genes whose expression is directly controlled by Gal4 and Ste12 as cells respond to changes in carbon source and mating pheromone, respectively. The results identify pathways that are coordinately regulated by each of the two activators and reveal previously unknown functions for Gal4 and Ste12. Genome-wide location analysis will facilitate investigation of gene regulatory networks, gene function, and genome maintenance.

1 Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
2 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3 Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4 Program in Molecular Biology University of Southern California, Los Angeles, CA 90089-1340, USA.
5 Corning, Inc., Corning, NY 14834, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: young{at}wi.mit.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A single transcription factor regulates evolutionarily diverse but functionally linked metabolic pathways in response to nutrient availability.
A. K. Schmid, D. J. Reiss, M. Pan, T. Koide, and N. S. Baliga (2014)
Mol Syst Biol 5, 282
   Abstract »    Full Text »    PDF »
Prevalence of transcription promoters within archaeal operons and coding sequences.
T. Koide, D. J. Reiss, J. C. Bare, W. L. Pang, M. T. Facciotti, A. K. Schmid, M. Pan, B. Marzolf, P. T. Van, F.-Y. Lo, et al. (2014)
Mol Syst Biol 5, 285
   Abstract »    Full Text »    PDF »
GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome.
M. D. Sekedat, D. Fenyo, R. S. Rogers, A. J. Tackett, J. D. Aitchison, and B. T. Chait (2014)
Mol Syst Biol 6, 353
   Abstract »    Full Text »    PDF »
Defining the budding yeast chromatin-associated interactome.
J.-P. Lambert, J. Fillingham, M. Siahbazi, J. Greenblatt, K. Baetz, and D. Figeys (2014)
Mol Syst Biol 6, 448
   Abstract »    Full Text »    PDF »
A systems biology approach to prediction of oncogenes and molecular perturbation targets in B-cell lymphomas.
K. M. Mani, C. Lefebvre, K. Wang, W. K. Lim, K. Basso, R. Dalla-Favera, and A. Califano (2014)
Mol Syst Biol 4, 169
   Abstract »    Full Text »    PDF »
From E-MAPs to module maps: dissecting quantitative genetic interactions using physical interactions.
I. Ulitsky, T. Shlomi, M. Kupiec, and R. Shamir (2014)
Mol Syst Biol 4, 209
   Abstract »    Full Text »    PDF »
Communication between levels of transcriptional control improves robustness and adaptivity.
A. M. Tsankov, C. R. Brown, M. C. Yu, M. Z. Win, P. A. Silver, and J. M. Casolari (2014)
Mol Syst Biol 2, 65
   Abstract »    Full Text »    PDF »
Reconstructing dynamic regulatory maps.
J. Ernst, O. Vainas, C. T. Harbison, I. Simon, and Z. Bar-Joseph (2014)
Mol Syst Biol 3, 74
   Abstract »    Full Text »    PDF »
Inferring condition-specific transcription factor function from DNA binding and gene expression data.
R. P. McCord, M. F. Berger, A. A. Philippakis, and M. L. Bulyk (2014)
Mol Syst Biol 3, 100
   Abstract »    Full Text »    PDF »
Transcriptional responses to fatty acid are coordinated by combinatorial control.
J. J. Smith, S. A. Ramsey, M. Marelli, B. Marzolf, D. Hwang, R. A. Saleem, R. A. Rachubinski, and J. D. Aitchison (2014)
Mol Syst Biol 3, 115
   Abstract »    Full Text »    PDF »
PhosphoPep--a phosphoproteome resource for systems biology research in Drosophila Kc167 cells.
B. Bodenmiller, J. Malmstrom, B. Gerrits, D. Campbell, H. Lam, A. Schmidt, O. Rinner, L. N. Mueller, P. T. Shannon, P. G. Pedrioli, et al. (2014)
Mol Syst Biol 3, 139
   Abstract »    Full Text »    PDF »
Integrative analysis of genome-wide experiments in the context of a large high-throughput data compendium.
A. Tanay, I. Steinfeld, M. Kupiec, and R. Shamir (2014)
Mol Syst Biol 1, 2005.0002
   Abstract »    Full Text »    PDF »
Differential network biology.
T. Ideker and N. J. Krogan (2014)
Mol Syst Biol 8, 565
   Abstract »    Full Text »    PDF »
Ancestral Resurrection of the Drosophila S2E Enhancer Reveals Accessible Evolutionary Paths through Compensatory Change.
C. Martinez, J. S. Rest, A.-R. Kim, M. Ludwig, M. Kreitman, K. White, and J. Reinitz (2014)
Mol. Biol. Evol. 31, 903-916
   Abstract »    Full Text »    PDF »
Large-Scale Quality Analysis of Published ChIP-seq Data.
G. K. Marinov, A. Kundaje, P. J. Park, and B. J. Wold (2014)
g3 4, 209-223
   Abstract »    Full Text »    PDF »
YTRP: a repository for yeast transcriptional regulatory pathways.
T.-H. Yang, C.-C. Wang, Y.-C. Wang, and W.-S. Wu (2014)
Database 2014, bau014
   Abstract »    Full Text »    PDF »
Systematic discovery and characterization of regulatory motifs in ENCODE TF binding experiments.
P. Kheradpour and M. Kellis (2014)
Nucleic Acids Res. 42, 2976-2987
   Abstract »    Full Text »    PDF »
Discrimination between thermodynamic models of cis-regulation using transcription factor occupancy data.
R. D. Zeigler and B. A. Cohen (2014)
Nucleic Acids Res. 42, 2224-2234
   Abstract »    Full Text »    PDF »
footprintDB: a database of transcription factors with annotated cis elements and binding interfaces.
A. Sebastian and B. Contreras-Moreira (2014)
Bioinformatics 30, 258-265
   Abstract »    Full Text »    PDF »
Covariation between homeodomain transcription factors and the shape of their DNA binding sites.
I. Dror, T. Zhou, Y. Mandel-Gutfreund, and R. Rohs (2014)
Nucleic Acids Res. 42, 430-441
   Abstract »    Full Text »    PDF »
Topology and Control of the Cell-Cycle-Regulated Transcriptional Circuitry.
S. B. Haase and C. Wittenberg (2014)
Genetics 196, 65-90
   Abstract »    Full Text »    PDF »
DPRP: a database of phenotype-specific regulatory programs derived from transcription factor binding data.
D. T. W. Tzeng, Y.-T. Tseng, M. Ung, I.-E. Liao, C.-C. Liu, and C. Cheng (2014)
Nucleic Acids Res. 42, D178-D183
   Abstract »    Full Text »    PDF »
Applications of alignment-free methods in epigenomics.
L. Pinello, G. Lo Bosco, and G.-C. Yuan (2013)
Brief Bioinform
   Abstract »    Full Text »    PDF »
Purification of a specific native genomic locus for proteomic analysis.
S. D. Byrum, S. D. Taverna, and A. J. Tackett (2013)
Nucleic Acids Res. 41, e195
   Abstract »    Full Text »    PDF »
Genome-wide analysis of Staufen-associated mRNAs identifies secondary structures that confer target specificity.
J. D. Laver, X. Li, K. Ancevicius, J. T. Westwood, C. A. Smibert, Q. D. Morris, and H. D. Lipshitz (2013)
Nucleic Acids Res. 41, 9438-9460
   Abstract »    Full Text »    PDF »
Identification of transcription factor binding sites from ChIP-seq data at high resolution.
A. F. Bardet, J. Steinmann, S. Bafna, J. A. Knoblich, J. Zeitlinger, and A. Stark (2013)
Bioinformatics 29, 2705-2713
   Abstract »    Full Text »    PDF »
Early Colony Establishment in Neurospora crassa Requires a MAP Kinase Regulatory Network.
A. C. Leeder, W. Jonkers, J. Li, and N. L. Glass (2013)
Genetics 195, 883-898
   Abstract »    Full Text »    PDF »
Pro-inflammatory cytokines can act as intracellular modulators of commensal bacterial virulence.
J. Mahdavi, P.-J. Royer, H. S. Sjolinder, S. Azimi, T. Self, J. Stoof, L. M. Wheldon, K. Brannstrom, R. Wilson, J. Moreton, et al. (2013)
Open Bio 3, 130048
   Abstract »    Full Text »    PDF »
Mapping Yeast Transcriptional Networks.
T. R. Hughes and C. G. de Boer (2013)
Genetics 195, 9-36
   Abstract »    Full Text »    PDF »
Next-generation sequencing technologies and their impact on microbial genomics.
B. M. Forde and P. W. O'Toole (2013)
Briefings in Functional Genomics 12, 440-453
   Abstract »    Full Text »    PDF »
DNA motif elucidation using belief propagation.
K.-C. Wong, T.-M. Chan, C. Peng, Y. Li, and Z. Zhang (2013)
Nucleic Acids Res. 41, e153
   Abstract »    Full Text »    PDF »
Mod5 protein binds to tRNA gene complexes and affects local transcriptional silencing.
M. Pratt-Hyatt, D. A. Pai, R. A. Haeusler, G. G. Wozniak, P. D. Good, E. L. Miller, I. X. McLeod, J. R. Yates III, A. K. Hopper, and D. R. Engelke (2013)
PNAS 110, E3081-E3089
   Abstract »    Full Text »    PDF »
Integrative analysis of C. elegans modENCODE ChIP-seq data sets to infer gene regulatory interactions.
E. L. Van Nostrand and S. K. Kim (2013)
Genome Res. 23, 941-953
   Abstract »    Full Text »    PDF »
ChIP-PED enhances the analysis of ChIP-seq and ChIP-chip data.
G. Wu, J. T. Yustein, M. N. McCall, M. Zilliox, R. A. Irizarry, K. Zeller, C. V. Dang, and H. Ji (2013)
Bioinformatics 29, 1182-1189
   Abstract »    Full Text »    PDF »
RNA-sequencing analysis of high glucose-treated monocytes reveals novel transcriptome signatures and associated epigenetic profiles.
F. Miao, Z. Chen, L. Zhang, J. Wang, H. Gao, X. Wu, and R. Natarajan (2013)
Physiol Genomics 45, 287-299
   Abstract »    Full Text »    PDF »
Nanobody(R)-based chromatin immunoprecipitation/micro-array analysis for genome-wide identification of transcription factor DNA binding sites.
T. Nguyen-Duc, E. Peeters, S. Muyldermans, D. Charlier, and G. Hassanzadeh-Ghassabeh (2013)
Nucleic Acids Res. 41, e59
   Abstract »    Full Text »    PDF »
Sparsely correlated hidden Markov models with application to genome-wide location studies.
H. Choi, D. Fermin, A. I. Nesvizhskii, D. Ghosh, and Z. S. Qin (2013)
Bioinformatics 29, 533-541
   Abstract »    Full Text »    PDF »
Systematic measurement of transcription factor-DNA interactions by targeted mass spectrometry identifies candidate gene regulatory proteins.
H. Mirzaei, T. A. Knijnenburg, B. Kim, M. Robinson, P. Picotti, G. W. Carter, S. Li, D. J. Dilworth, J. K. Eng, J. D. Aitchison, et al. (2013)
PNAS 110, 3645-3650
   Abstract »    Full Text »    PDF »
Genome-scale bacterial transcriptional regulatory networks: reconstruction and integrated analysis with metabolic models.
J. P. Faria, R. Overbeek, F. Xia, M. Rocha, I. Rocha, and C. S. Henry (2013)
Brief Bioinform
   Abstract »    Full Text »    PDF »
The twilight zone of cis element alignments.
A. Sebastian and B. Contreras-Moreira (2013)
Nucleic Acids Res. 41, 1438-1449
   Abstract »    Full Text »    PDF »
MuMoD: a Bayesian approach to detect multiple modes of protein-DNA binding from genome-wide ChIP data.
L. Narlikar (2013)
Nucleic Acids Res. 41, 21-32
   Abstract »    Full Text »    PDF »
A novel ab initio identification system of transcriptional regulation motifs in genome DNA sequences based on direct comparison scheme of signal/noise distributions.
R. Nakaki, J. Kang, and M. Tateno (2012)
Nucleic Acids Res. 40, 8835-8848
   Abstract »    Full Text »    PDF »
Uncovering Transcription Factor Modules Using One- and Three-dimensional Analyses.
(2012)
J. Biol. Chem. 287, 30914-30921
Genome-wide Epigenetic Data Facilitate Understanding of Disease Susceptibility Association Studies.
(2012)
J. Biol. Chem. 287, 30932-30940
Understanding transcriptional regulation by integrative analysis of transcription factor binding data.
C. Cheng, R. Alexander, R. Min, J. Leng, K. Y. Yip, J. Rozowsky, K.-K. Yan, X. Dong, S. Djebali, Y. Ruan, et al. (2012)
Genome Res. 22, 1658-1667
   Abstract »    Full Text »    PDF »
ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia.
S. G. Landt, G. K. Marinov, A. Kundaje, P. Kheradpour, F. Pauli, S. Batzoglou, B. E. Bernstein, P. Bickel, J. B. Brown, P. Cayting, et al. (2012)
Genome Res. 22, 1813-1831
   Abstract »    Full Text »    PDF »
Interpreting the regulatory genome: the genomics of transcription factor function in Drosophila melanogaster.
M. Slattery, N. Negre, and K. P. White (2012)
Briefings in Functional Genomics 11, 336-346
   Abstract »    Full Text »    PDF »
Toward the identification and regulation of the Arabidopsis thaliana ABI3 regulon.
G. Monke, M. Seifert, J. Keilwagen, M. Mohr, I. Grosse, U. Hahnel, A. Junker, B. Weisshaar, U. Conrad, H. Baumlein, et al. (2012)
Nucleic Acids Res. 40, 8240-8254
   Abstract »    Full Text »    PDF »
Considerations for creating and annotating the budding yeast Genome Map at SGD: a progress report.
E. T. Chan and J. M. Cherry (2012)
Database 2012, bar057
   Abstract »    Full Text »    PDF »
Improved Models for Transcription Factor Binding Site Identification Using Nonindependent Interactions.
Y. Zhao, S. Ruan, M. Pandey, and G. D. Stormo (2012)
Genetics 191, 781-790
   Abstract »    Full Text »    PDF »
Make way for the 'next generation': application and prospects for genome-wide, epigenome-specific technologies in endocrine research.
R. D. Emes and W. E. Farrell (2012)
J. Mol. Endocrinol. 49, R19-R27
   Abstract »    Full Text »    PDF »
Characterizing the roles of Met31 and Met32 in coordinating Met4-activated transcription in the absence of Met30.
E. Carrillo, G. Ben-Ari, J. Wildenhain, M. Tyers, D. Grammentz, and T. A. Lee (2012)
Mol. Biol. Cell 23, 1928-1942
   Abstract »    Full Text »    PDF »
Profiles of Epigenetic Histone Post-translational Modifications at Type 1 Diabetes Susceptible Genes.
F. Miao, Z. Chen, L. Zhang, Z. Liu, X. Wu, Y.-C. Yuan, and R. Natarajan (2012)
J. Biol. Chem. 287, 16335-16345
   Abstract »    Full Text »    PDF »
A workflow for genome-wide mapping of archaeal transcription factors with ChIP-seq.
E. G. Wilbanks, D. J. Larsen, R. Y. Neches, A. I. Yao, C.-Y. Wu, R. A. S. Kjolby, and M. T. Facciotti (2012)
Nucleic Acids Res. 40, e74
   Abstract »    Full Text »    PDF »
Young intragenic miRNAs are less coexpressed with host genes than old ones: implications of miRNA-host gene coevolution.
C. He, Z. Li, P. Chen, H. Huang, L. D. Hurst, and J. Chen (2012)
Nucleic Acids Res. 40, 4002-4012
   Abstract »    Full Text »    PDF »
A rapid assay for affinity and kinetics of molecular interactions with nucleic acids.
G. P. Donaldson, K. G. Roelofs, Y. Luo, H. O. Sintim, and V. T. Lee (2012)
Nucleic Acids Res. 40, e48
   Abstract »    Full Text »    PDF »
A negative feedback loop at the nuclear periphery regulates GAL gene expression.
E. M. Green, Y. Jiang, R. Joyner, and K. Weis (2012)
Mol. Biol. Cell 23, 1367-1375
   Abstract »    Full Text »    PDF »
De novo motif discovery facilitates identification of interactions between transcription factors in Saccharomyces cerevisiae.
M.-J. M. Chen, L.-C. Chou, T.-T. Hsieh, D.-D. Lee, K.-W. Liu, C.-Y. Yu, Y.-J. Oyang, H.-K. Tsai, and C.-Y. Chen (2012)
Bioinformatics 28, 701-708
   Abstract »    Full Text »    PDF »
Analysis of Gal4-directed transcription activation using Tra1 mutants selectively defective for interaction with Gal4.
L. Lin, L. Chamberlain, L. J. Zhu, and M. R. Green (2012)
PNAS 109, 1997-2002
   Abstract »    Full Text »    PDF »
YeTFaSCo: a database of evaluated yeast transcription factor sequence specificities.
C. G. de Boer and T. R. Hughes (2012)
Nucleic Acids Res. 40, D169-D179
   Abstract »    Full Text »    PDF »
The Conserved Foot Domain of RNA Pol II Associates with Proteins Involved in Transcriptional Initiation and/or Early Elongation.
M. C. Garcia-Lopez, V. Pelechano, M. C. Miron-Garcia, A. I. Garrido-Godino, A. Garcia, O. Calvo, M. Werner, J. E. Perez-Ortin, and F. Navarro (2011)
Genetics 189, 1235-1248
   Abstract »    Full Text »    PDF »
H3K4 tri-methylation provides an epigenetic signature of active enhancers.
A. Pekowska, T. Benoukraf, J. Zacarias-Cabeza, M. Belhocine, F. Koch, H. Holota, J. Imbert, J.-C. Andrau, P. Ferrier, and S. Spicuglia (2011)
EMBO J. 30, 4198-4210
   Abstract »    Full Text »    PDF »
Role of ZBP-89 in human globin gene regulation and erythroid differentiation.
A. J. Woo, J. Kim, J. Xu, H. Huang, and A. B. Cantor (2011)
Blood 118, 3684-3693
   Abstract »    Full Text »    PDF »
In vitro DNA-binding profile of transcription factors: methods and new insights.
J. Wang, J. Lu, G. Gu, and Y. Liu (2011)
J. Endocrinol. 210, 15-27
   Abstract »    Full Text »    PDF »
A Novel Specificity Protein 1 (SP1)-like Gene Regulating Protein Kinase C-1 (Pkc1)-dependent Cell Wall Integrity and Virulence Factors in Cryptococcus neoformans.
A. Adler, Y.-D. Park, P. Larsen, V. Nagarajan, K. Wollenberg, J. Qiu, T. G. Myers, and P. R. Williamson (2011)
J. Biol. Chem. 286, 20977-20990
   Abstract »    Full Text »    PDF »
Epigenetic mechanisms in diabetic vascular complications.
M. A. Reddy and R. Natarajan (2011)
Cardiovasc Res 90, 421-429
   Abstract »    Full Text »    PDF »
hmChIP: a database and web server for exploring publicly available human and mouse ChIP-seq and ChIP-chip data.
L. Chen, G. Wu, and H. Ji (2011)
Bioinformatics 27, 1447-1448
   Abstract »    Full Text »    PDF »
Medusa structure of the gene regulatory network: dominance of transcription factors in cancer subtype classification.
Y. Guo, Y. Feng, N. S. Trivedi, and S. Huang (2011)
Experimental Biology and Medicine 236, 628-636
   Abstract »    Full Text »    PDF »
Calling Cards enable multiplexed identification of the genomic targets of DNA-binding proteins.
H. Wang, D. Mayhew, X. Chen, M. Johnston, and R. D. Mitra (2011)
Genome Res. 21, 748-755
   Abstract »    Full Text »    PDF »
Characterization of Protein-DNA Interactions Using Protein Microarrays.
S. Hu, Z. Xie, S. Blackshaw, J. Qian, and H. Zhu (2011)
Cold Spring Harb Protoc 2011, pdb.prot5614
   Abstract »    Full Text »    PDF »
Two transcription factors are necessary for iron homeostasis in a salt-dwelling archaeon.
A. K. Schmid, M. Pan, K. Sharma, and N. S. Baliga (2011)
Nucleic Acids Res. 39, 2519-2533
   Abstract »    Full Text »    PDF »
ChIP-on-chip analysis reveals angiopoietin 2 (Ang2, ANGPT2) as a novel target of steroidogenic factor-1 (SF-1, NR5A1) in the human adrenal gland.
B. Ferraz-de-Souza, L. Lin, S. Shah, N. Jina, M. Hubank, M. T. Dattani, and J. C. Achermann (2011)
FASEB J 25, 1166-1175
   Abstract »    Full Text »    PDF »
EpiChIP: gene-by-gene quantification of epigenetic modification levels.
D. Hebenstreit, M. Gu, S. Haider, D. J. Turner, P. Lio, and S. A. Teichmann (2011)
Nucleic Acids Res. 39, e27
   Abstract »    Full Text »    PDF »
Sensitive and accurate identification of protein-DNA binding events in ChIP-chip assays using higher order derivative analysis.
C. L. Barrett, B.-K. Cho, and B. O. Palsson (2011)
Nucleic Acids Res. 39, 1656-1665
   Abstract »    Full Text »    PDF »
Sequential Recruitment of SAGA and TFIID in a Genomic Response to DNA Damage in Saccharomyces cerevisiae.
S. Ghosh and B. F. Pugh (2011)
Mol. Cell. Biol. 31, 190-202
   Abstract »    Full Text »    PDF »
FlyFactorSurvey: a database of Drosophila transcription factor binding specificities determined using the bacterial one-hybrid system.
L. J. Zhu, R. G. Christensen, M. Kazemian, C. J. Hull, M. S. Enuameh, M. D. Basciotta, J. A. Brasefield, C. Zhu, Y. Asriyan, D. S. Lapointe, et al. (2011)
Nucleic Acids Res. 39, D111-D117
   Abstract »    Full Text »    PDF »
Innovative technology for cancer risk analysis.
S. Tommas, K. Danza, B. Pilato, and S. De Summa (2011)
Ann. Onc. 22, i37-i43
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882