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 325 (5939): 429-432

Copyright © 2009 by the American Association for the Advancement of Science

Transcriptional Regulatory Circuits: Predicting Numbers from Alphabets

Harold D. Kim,1,* Tal Shay,2,* Erin K. O’Shea,1 Aviv Regev2,{dagger}

Abstract: Transcriptional regulatory circuits govern how cis and trans factors transform signals into messenger RNA (mRNA) expression levels. With advances in quantitative and high-throughput technologies that allow measurement of gene expression state in different conditions, data that can be used to build and test models of transcriptional regulation is being generated at a rapid pace. Here, we review experimental and computational methods used to derive detailed quantitative circuit models on a small scale and cruder, genome-wide models on a large scale. We discuss the potential of combining small- and large-scale approaches to understand the working and wiring of transcriptional regulatory circuits.

1 Howard Hughes Medical Institute, Harvard University Faculty of Arts and Sciences Center for Systems Biology, Departments of Molecular and Cellular Biology and Chemistry and Chemical Biology, Cambridge, MA 02138, USA.
2 Department of Biology, Massachusetts Institute of Technology, and Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

* These authors contributed equally to this work.

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

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Analysis of CDS-located miRNA target sites suggests that they can effectively inhibit translation.
J. Hausser, A. P. Syed, B. Bilen, and M. Zavolan (2013)
Genome Res. 23, 604-615
   Abstract »    Full Text »    PDF »
Transcriptional modulation of the developing immune system by early life social adversity.
S. W. Cole, G. Conti, J. M. G. Arevalo, A. M. Ruggiero, J. J. Heckman, and S. J. Suomi (2012)
PNAS 109, 20578-20583
   Abstract »    Full Text »    PDF »
Ultrashort and progressive 4sU-tagging reveals key characteristics of RNA processing at nucleotide resolution.
L. Windhager, T. Bonfert, K. Burger, Z. Ruzsics, S. Krebs, S. Kaufmann, G. Malterer, A. L'Hernault, M. Schilhabel, S. Schreiber, et al. (2012)
Genome Res. 22, 2031-2042
   Abstract »    Full Text »    PDF »
Quantitative Analysis of the Bidirectional Viral G-Protein-Coupled Receptor and Lytic Latency-Associated Nuclear Antigen Promoter of Kaposi's Sarcoma-Associated Herpesvirus.
I. B. Hilton and D. P. Dittmer (2012)
J. Virol. 86, 9683-9695
   Abstract »    Full Text »    PDF »
Global identification of transcriptional regulators of pluripotency and differentiation in embryonic stem cells.
K.-J. Won, Z. Xu, X. Zhang, J. W. Whitaker, R. Shoemaker, B. Ren, Y. Xu, and W. Wang (2012)
Nucleic Acids Res. 40, 8199-8209
   Abstract »    Full Text »    PDF »
Learning transcriptional regulation on a genome scale: a theoretical analysis based on gene expression data.
M. Wu and C. Chan (2012)
Brief Bioinform 13, 150-161
   Abstract »    Full Text »    PDF »
Express Path Analysis Identifies a Tyrosine Kinase Src-centric Network Regulating Divergent Host Responses to Mycobacterium tuberculosis Infection.
A. F. Karim, P. Chandra, A. Chopra, Z. Siddiqui, A. Bhaskar, A. Singh, and D. Kumar (2011)
J. Biol. Chem. 286, 40307-40319
   Abstract »    Full Text »    PDF »
Conservation of transcription factor binding events predicts gene expression across species.
M. Hemberg and G. Kreiman (2011)
Nucleic Acids Res. 39, 7092-7102
   Abstract »    Full Text »    PDF »
Fine-tuning of the Msn2/4-mediated yeast stress responses as revealed by systematic deletion of Msn2/4 partners.
A. Sadeh, N. Movshovich, M. Volokh, L. Gheber, and A. Aharoni (2011)
Mol. Biol. Cell 22, 3127-3138
   Abstract »    Full Text »    PDF »
Comparing Signaling Networks between Normal and Transformed Hepatocytes Using Discrete Logical Models.
J. Saez-Rodriguez, L. G. Alexopoulos, M. Zhang, M. K. Morris, D. A. Lauffenburger, and P. K. Sorger (2011)
Cancer Res. 71, 5400-5411
   Abstract »    Full Text »    PDF »
Transcriptional regulation via TF-modifying enzymes: an integrative model-based analysis.
L. J. Everett, S. T. Jensen, and S. Hannenhalli (2011)
Nucleic Acids Res. 39, e78
   Abstract »    Full Text »    PDF »
Physical Module Networks: an integrative approach for reconstructing transcription regulation.
N. Novershtern, A. Regev, and N. Friedman (2011)
Bioinformatics 27, i177-i185
   Abstract »    Full Text »    PDF »
Experimental strategies for studying transcription factor-DNA binding specificities.
M. Geertz and S. J. Maerkl (2010)
Briefings in Functional Genomics 9, 362-373
   Abstract »    Full Text »    PDF »
Biological role of noise encoded in a genetic network motif.
M. Kittisopikul and G. M. Suel (2010)
PNAS 107, 13300-13305
   Abstract »    Full Text »    PDF »
Bacteria determine fate by playing dice with controlled odds.
E. Ben-Jacob and D. Schultz (2010)
PNAS 107, 13197-13198
   Full Text »    PDF »
Precise temporal control of the eye regulatory gene Pax6 via enhancer-binding site affinity.
S. Rowan, T. Siggers, S. A. Lachke, Y. Yue, M. L. Bulyk, and R. L. Maas (2010)
Genes & Dev. 24, 980-985
   Abstract »    Full Text »    PDF »
A Gluconeogenic Tryst in the Nucleus, with ER Stress as the Third Wheel.
D. T. Rutkowski (2009)
Science Signaling 2, pe72
   Abstract »    Full Text »    PDF »
Unbiased Reconstruction of a Mammalian Transcriptional Network Mediating Pathogen Responses.
I. Amit, M. Garber, N. Chevrier, A. P. Leite, Y. Donner, T. Eisenhaure, M. Guttman, J. K. Grenier, W. Li, O. Zuk, et al. (2009)
Science 326, 257-263
   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