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.
A Systems Approach to Mapping DNA Damage Response Pathways
Christopher T. Workman,1*H. Craig Mak,1*Scott McCuine,1Jean-Bosco Tagne,2Maya Agarwal,1Owen Ozier,2Thomas J. Begley,3Leona D. Samson,4Trey Ideker1
Failure of cells to respond to DNA damage is a primary eventassociated with mutagenesis and environmental toxicity. To mapthe transcriptional network controlling the damage response,we measured genomewide binding locations for 30 damage-relatedtranscription factors (TFs) after exposure of yeast to methyl-methanesulfonate(MMS). The resulting 5272 TF-target interactions revealed extensivechanges in the pattern of promoter binding and identified damage-specificbinding motifs. As systematic functional validation, we identifiedinteractions for which the target changed expression in wild-typecells in response to MMS but was nonresponsive in cells lackingthe TF. Validated interactions were assembled into causal pathwaymodels that provide global hypotheses of how signaling, transcription,and phenotype are integrated after damage.
1 University of California San Diego, La Jolla, CA 92093, USA. 2 Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA. 3 University of AlbanyState University at New York, Rensselaer, NY 12144, USA. 4 Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: trey{at}bioeng.ucsd.edu
Direct targets of the TRP63 transcription factor revealed by a combination of gene expression profiling and reverse engineering.
G. Della Gatta, M. Bansal, A. Ambesi-Impiombato, D. Antonini, C. Missero, and D. di Bernardo (2008)
Genome Res.
18, 939-948
|Abstract »|Full Text »|PDF »
Discovering Regulators of the Drosophila Cardiac Hypoxia Response Using Automated Phenotyping Technology.
J. D. FEALA, J. H. OMENS, G. PATERNOSTRO, and A. D. MCCULLOCH (2008)
Ann. N.Y. Acad. Sci.
1123, 169-177
|Abstract »|Full Text »|PDF »
A systems approach to delineate functions of paralogous transcription factors: Role of the Yap family in the DNA damage response.
K. Tan, H. Feizi, C. Luo, S. H. Fan, T. Ravasi, and T. G. Ideker (2008)
PNAS
105, 2934-2939
|Abstract »|Full Text »|PDF »
YEASTRACT-DISCOVERER: new tools to improve the analysis of transcriptional regulatory associations in Saccharomyces cerevisiae.
P. T. Monteiro, N. D. Mendes, M. C. Teixeira, S. d'Orey, S. Tenreiro, N. P. Mira, H. Pais, A. P. Francisco, A. M. Carvalho, A. B. Lourenco, et al. (2008)
Nucleic Acids Res.
36, D132-D136
|Abstract »|Full Text »|PDF »
Learning Regulatory Programs That Accurately Predict Differential Expression with MEDUSA.
A. KUNDAJE, S. LIANOGLOU, X. LI, D. QUIGLEY, M. ARIAS, C. H. WIGGINS, L. ZHANG, and C. LESLIE (2007)
Ann. N.Y. Acad. Sci.
1115, 178-202
|Abstract »|Full Text »|PDF »
SPINE: a framework for signaling-regulatory pathway inference from cause-effect experiments.
O. Ourfali, T. Shlomi, T. Ideker, E. Ruppin, and R. Sharan (2007)
Bioinformatics
23, i359-i366
|Abstract »|Full Text »|PDF »
Interpreting physiological responses to environmental change through gene expression profiling.