Network motifs: Theory and experimental approaches

Nature Reviews Genetics

Volumn 8, Issue 6, 2007, Pages 450-461

  Alon, Uri ^a  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOREGULATION; EXPERIMENTAL STUDY; GENE FUNCTION; GENETIC REGULATION; HUMAN; MOLECULAR DYNAMICS; MOLECULAR EVOLUTION; NERVE CELL NETWORK; NONHUMAN; POSITIVE FEEDBACK; PRIORITY JOURNAL; PULSE GENERATOR; REGULON; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION;

ANIMALS; BACTERIA; EVOLUTION; FUNGI; GENE EXPRESSION REGULATION; HOMEOSTASIS; HUMANS; MODELS, GENETIC; REGULON; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

BACTERIA (MICROORGANISMS);

EID: 34249079154     PISSN: 14710056     EISSN: 14710064     Source Type: Journal    
DOI: 10.1038/nrg2102     Document Type: Review

References (100)

1. Alon, U. Introduction to Systems Biology: Design Principles Of Biological Circuits (CRC, Boca Raton, 2006).
2. Davidson, E. H. The Regulatory Genome: Gene Regulatory Networks In Development And Evolution, (Academic, Burlington, 2006).
3. Ptashne, M. & Gann, A. Genes & Signals (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2002).
4. Levine, M. & Davidson, E. H. Gene regulatory networks for development. Proc. Natl Acad. Sci. USA 102, 4936-4942 (2005).
5. Thieffry, D., Huerta, A. M., Perez-Rueda, E. & Collado-Vides, J. From specific gene regulation to genomic networks: a global analysis of transcriptional regulation in Escherichia coli. Bioessays 20, 433-440 (1998).
6. Shen-Orr, S. S., Milo, R., Mangan, S. & Alon, U. Network motifs in the transcriptional regulation network of Escherichia coli. Nature Genet. 31, 64-68 (2002).
7. Milo, R. et al. Network motifs: simple building blocks of complex networks. Science 298, 824-827 (2002).
8. Eichenberger, P. et al. The program of gene transcription for a single differentiating cell type during sporulation in Bacillus subtilis. PLoS Biol. 2, e328 (2004).
9. Mangan, S., Zaslaver, A. & Alon, U. The coherent feedforward loop serves as a sign-sensitive delay element in transcription networks. J. Mol. Biol. 334, 197-204 (2003).
10. Lee, T. I. et al. Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 298, 799-804 (2002).
11. Odom, D. T. et al. Control of pancreas and liver gene expression by HNF transcription factors. Science 303, 1378-1381 (2004).
12. Boyer, L. A. et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122, 947-956 (2005).
13. Saddic, L. A. et al. The LEAFY target LMI1 is a meristem identity regulator and acts together with LEAFY to regulate expression of CAULIFLOWER. Development 133, 1673-1682 (2006).
14. Swiers, G., Patient, R. & Loose, M. Genetic regulatory networks programming hematopoietic stem cells and erythroid lineage specification. Dev. Biol. 294, 525-540 (2006).
15. Iranfar, N., Fuller, D. & Loomis, W. F. Transcriptional regulation of post-aggregation genes in Dictyostelium by a feed-forward loop involving GBF and LagC. Dev. Biol. 290, 460-469 (2006).
16. Milo, R. et al. Superfamilies of designed and evolved networks. Science 303, 1538-1542 (2004).
17. Rosenfeld, N., Elowitz, M. B. & Alon, U. Negative autoregulation speeds the response times of transcription networks. J. Mol. Biol. 323, 785-793 (2002).
18. Savageau, M. A. Comparison of classical and autogenous systems of regulation in inducible operons. Nature 252, 546-549 (1974).
19. Becskei, A. & Serrano, L. Engineering stability in gene networks by autoregulation. Nature 405, 590-593 (2000).
20. Camas, F. M., Blazquez, J. & Poyatos, J. F. Autogenous and nonautogenous control of response in a genetic network. Proc. Natl Acad. Sci. USA 103, 12718-12723 (2006).
21. Zaslaver, A. et al. A comprehensive library of fluorescent transcriptional reporters for Escherichia coli. Nature Methods 3, 623-628 (2006).
22. Kaern, M., Elston, T. C., Blake, W. J. & Collins, J. J. Stochasticity in gene expression: from theories to phenotypes. Nature Rev. Genet. 6, 451-464 (2005).
23. Dublanche, Y., Michalodimitrakis, K., Kummerer, N., Foglierini, M. & Serrano, L. Noise in transcription negative feedback loops: simulation and experimental analysis. Mol. Syst. Biol. 2, 41 (2006).
24. Kalir, S., Mangan, S. & Alon, U. The coherent feed-forward loop with a SUM input function prolongs flagella production in Escherichia coli. Mol. Syst. Biol. 1, 2005.0006 (2005).
25. Maeda, Y. T. & Sano, M. Regulatory dynamics of synthetic gene networks with positive feedback. J. Mol. Biol. 359, 1107-1124 (2006).
26. Becskei, A., Seraphin, B. & Serrano, L. Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion. EMBO J. 20, 2528-2535 (2001).
27. Kramer, B. P. & Fussenegger, M. Hysteresis in a synthetic mammalian gene network. Proc. Natl Acad. Sci. USA 102, 9517-9522 (2005).
28. Wolf, D. M. & Arkin, A. P. Motifs, modules and games in bacteria. Curr. Opin. Microbiol. 6, 125-134 (2003).
29. Yuh, C. H., Bolouri, H. & Davidson, E. H. Genomic cis-regulatory logic: experimental and computational analysis of a sea urchin gene. Science 279, 1896-1902 (1998).
30. Buchler, N. E., Gerland, U. & Hwa, T. On schemes of combinatorial transcription logic. Proc. Natl Acad. Sci. USA 100, 5136-5141 (2003).
31. Kalir, S. & Alon, U. Using a quantitative blueprint to reprogram the dynamics of the flagella gene network. Cell 117, 713-720 (2004).
32. Setty, Y., Mayo, A. E., Surette, M. G. & Alon, U. Detailed map of a cis-regulatory input function. Proc. Natl Acad. Sci. USA 100, 7702-7707 (2003).
33. Ma, H. W. et al. An extended regulatory network of Escherichia coli and analysis of its hierarchical structure and network motifs. Nucleic Acids Res. 32, 6643-6649 (2004).
34. Mangan, S. & Alon, U. Structure and function of the feed-forward loop network motif. Proc. Natl Acad. Sci. USA 100, 11980-11985 (2003).
35. Basu, S., Mehreja, R., Thiberge, S., Chen, M. T. & Weiss, R. Spatiotemporal control of gene expression with pulse-generating networks. Proc. Natl Acad. Sci. USA 101, 6355-6360 (2004).
36. Mangan, S., Zaslaver, A. & Alon, U. The incoherent feed-forward loop accelerates the response-time of the gal system of Escherichia coli. J. Mol. Biol. 356, 1073-1081 (2006).
37. Hornstein, E. & Shomron, N. Canalization of development by microRNAs. Nature Genet. 38, S20-S24 (2006).
38. O'Donnell, K. A., Wentzel, E. A., Zeller, K. I., Dang, C. V. & Mendell, J. T. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435, 839-843 (2005).
39. Johnston, R. J. Jr. et al. An unusual Zn-finger/FH2 domain protein controls a left/right asymmetric neuronal fate decision in C. elegans. Development 133, 3317-3328 (2006).
40. Ghosh, B., Karmakar, R. & Bose, I. Noise characteristics of feed forward loops. Phys. Biol. 2, 36-45 (2005).
41. Wall, M. E., Dunlop, M. J. & Hlavacek, W. S. Multiple functions of a feed-forward-loop gene circuit. J. Mol. Biol. 349, 501-514 (2005).
42. Hayot, F. & Jayaprakash, C. A feedforward loop motif in transcriptional regulation: induction and repression. J. Theor. Biol. 234, 133-143 (2005).
43. Ishihara, S., Fujimoto, K. & Shibata, T. Cross talking of network motifs in gene regulation that generates temporal pulses and spatial stripes. Genes Cells 10, 1025-1038 (2005).
44. Kashtan, N., Itzkovitz, S., Milo, R. & Alon, U. Topological generalizations of network motifs. Phys. Rev. E 70, 031909 (2004).
45. Dobrin, R., Beg, Q. K., Barabasi, A. L. & Oltvai, Z. N. Aggregation of topological motifs in the Escherichia coli transcriptional regulatory network. BMC Bioinformatics 5, 10 (2004).
46. Ronen, M., Rosenberg, R., Shraiman, B. I. & Alon, U. Assigning numbers to the arrows: parameterizing a gene regulation network by using accurate expression kinetics. Proc. Natl Acad. Sci. USA 99, 10555-10560 (2002).
47. Zaslaver, A. et al. Just-in-time transcription program in metabolic pathways. Nature Genet. 36, 486-491 (2004).
48. Kalir, S. et al. Ordering genes in a flagella pathway by analysis of expression kinetics from living bacteria. Science 292, 2080-2083 (2001).
49. Laub, M. T., McAdams, H. H., Feldblyum, T., Fraser, C. M. & Shapiro, L. Global analysis of the genetic network controlling a bacterial cell cycle. Science 290, 2144-2148 (2000).
50. McAdams, H. H. & Shapiro, L. A bacterial cell-cycle regulatory network operating in time and space. Science 301, 1874-1877 (2003).
51. Spellman, P. T. et al. Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol. Biol. Cell 9, 3273-3297 (1998).
52. Ingram, P. J., Stumpf, M. P., Stark, J. Network motifs: structure does not determine function. BMC Genomics 5, 108 (2006).
53. Pilpel, Y., Sudarsanam, P. & Church, G. M. Identifying regulatory networks by combinatorial analysis of promoter elements. Nature Genet. 29, 153-159 (2001).
54. Beer, M. & Tavazoie, S. Predicting gene expression from sequence. Cell 117, 185-198 (2004).
55. Rosenfeld, N. & Alon, U. Response delays and the structure of transcription networks. J. Mol. Biol. 329, 645-654 (2003).
56. Babu, M. M., Luscombe, N. M., Aravind, L., Gerstein, M. & Teichmann, S. A. Structure and evolution of transcriptional regulatory networks. Curr. Opin. Struct. Biol. 14, 283-291 (2004).
57. Yu, H., Luscombe, N. M., Qian, J. & Gerstein, M. Genomic analysis of gene expression relationships in transcriptional regulatory networks. Trends Genet. 19, 422-427 (2003).
58. Luscombe, N. M. et al. Genomic analysis of regulatory network dynamics reveals large topological changes. Nature 431, 308-312 (2004).
59. Amit, I. et al. A module of negative feedback regulators defines growth factor signaling. Nature Genet. 39, 503-512 (2007).
60. Davidson, E. H. et al. A genomic regulatory network for development. Science 295, 1669-1678 (2002).
61. Longabaugh, W. J., Davidson, E. H. & Bolouri, H. Computational representation of developmental genetic regulatory networks. Dev. Biol. 283, 1-16 (2005).
62. Johnston, R. J. Jr, Chang, S., Etchberger, J. F., Ortiz, C. O. & Hobert, O. MicroRNAs acting in a double-negative feedback loop to control a neuronal cell fate decision. Proc. Natl Acad. Sci. USA 102, 12449-12454 (2005).
63. Xiong, W. & Ferrell, J. E. Jr. A positive-feedback-based bistable 'memory module' that governs a cell fate decision. Nature 426, 460-465 (2003).
64. Brandman, O., Ferrell, J. E. Jr, Li, R. & Meyer, T. Interlinked fast and slow positive feedback loops drive reliable cell decisions. Science 310, 496-498 (2005).
65. Gardner, T. S., Cantor, C. R. & Collins, J. J. Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339-342 (2000).
66. Bolouri, H. & Davidson, E. H. Transcriptional regulatory cascades in development: initial rates, not steady state, determine network kinetics. Proc. Natl Acad. Sci. USA 100, 9371-9376 (2003).
67. Hooshangi, S., Thiberge, S. & Weiss, R. Ultrasensitivity and noise propagation in a synthetic transcriptional cascade. Proc. Natl Acad. Sci. USA 102, 3581-3586 (2005).
68. Rappaport, N., Winter, S. & Barkai, N. The ups and downs of biological timers. Theor. Biol. Med. Model. 2, 22 (2005).
69. Conant, G. C. & Wagner, A. Convergent evolution of gene circuits. Nature Genet. 34, 264-266 (2003).
70. Dekel, E. & Alon, U. Optimality and evolutionary tuning of the expression level of a protein. Nature 436, 588-592 (2005).
71. Ihmels, J. et al. Rewiring of the yeast transcriptional network through the evolution of motif usage. Science 309, 938-940 (2005).
72. Madan Babu, M., Teichmann, S. A. & Aravind, L. Evolutionary dynamics of prokaryotic transcriptional regulatory networks. J. Mol. Biol. 358, 614-633 (2006).
73. Dekel, E., Mangan, S. & Alon, U. Environmental selection of the feed-forward loop circuit in gene-regulation networks. Phys. Biol. 2, 81-88 (2005).
74. Prill, R. J., Iglesias, P. A. & Levchenko, A. Dynamic properties of network motifs contribute to biological network organization. PLoS Biol. 3, e343 (2005).
75. Kashtan, N., Itzkovitz, S., Milo, R. & Alon, U. Efficient sampling algorithm for estimating subgraph concentrations and detecting network motifs. Bioinformatics 20, 1746-1758 (2004).
76. Yeger-Lotem, E. et al. Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction. Proc. Natl Acad. Sci. USA 101, 5934-5939 (2004).
77. Zhang, L. V. et al. Motifs, themes and thematic maps of an integrated Saccharomyces cerevisiae interaction network. J. Biol. 4, 6 (2005).
78. Elowitz, M. B. & Leibler, S. A synthetic oscillatory network of transcriptional regulators. Nature 403, 335-338 (2000).
79. Lahav, G. et al. Dynamics of the p53-Mdm2 feedback loop in individual cells. Nature Genet. 36, 147-150 (2004).
80. Friedman, N., Vardi, S., Ronen, M., Alon, U. & Stavans, J. Precise temporal modulation in the response of the SOS DNA repair network in individual bacteria. PLoS Biol. 3, e238 (2005).
81. Hoffmann, A., Levchenko, A., Scott, M. L. & Baltimore, D. The IκB-NF-κB signaling module: temporal control and selective gene activation. Science 298, 1241-1245 (2002).
82. Nelson, D. E. et al. Oscillations in NF-κB signaling control the dynamics of gene expression. Science 306, 704-708 (2004).
83. Barkai, N. & Leibler, S. Circadian clocks limited by noise. Nature 403, 267-268 (2000).
84. Tyson, J. J., Chen, K. C. & Novak, B. Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. Curr. Opin. Cell Biol. 15, 221-231 (2003).
85. Tyson, J. J., Csikasz-Nagy, A. & Novak, B. The dynamics of cell cycle regulation. Bioessays 24, 1095-1109 (2002).
86. Pomerening, J. R., Sontag, E. D. & Ferrell, J. E. Jr. Building a cell cycle oscillator: hysteresis and bistability in the activation of Cdc2. Nature Cell Biol. 5, 346-351 (2003).
87. Suel, G. M., Garcia-Ojalvo, J., Liberman, L. M. & Elowitz, M. B. An excitable gene regulatory circuit induces transient cellular differentiation. Nature 440, 545-550 (2006).
88. Ptacek, J. et al. Global analysis of protein phosphorylation in yeast. Nature 438, 679-684 (2005).
89. Itzkovitz, S. et al. Coarse-graining and self-dissimilarity of complex networks. Phys. Rev. E 71, 016127 (2005).
90. Ma'ayan, A. et al. Formation of regulatory patterns during signal propagation in a mammalian cellular network. Science 309, 1078-1083 (2005).
91. Hertz, J., Krogh, A. & Palmer, R. G. Introduction to the Theory of Neural Computation (Perseus Books, Boulder, 1991).
92. Bray, D. Protein molecules as computational elements in living cells. Nature 376, 307-312 (1995).
93. Lund, R. D. Synaptic patterns of the superficial layers of the superior colliculus of the rat. J. Comp. Neurol. 135, 179-208 (1969).
94. White, E. L. Cortical Circuits (Birkhauser, Boston, 1989).
95. White, J., Southgate, E., Thomson, J. & Brenner, S. The nervous system of Caenorhabditis elegans. Philos. Trans. R. Soc. London B Biol. Sci. 314, 1 (1986).
96. Itzkovitz, S. & Alon, U. Subgraphs and network motifs in geometric networks. Phys. Rev. E 71, 026117 (2005).
97. Sporns, O. & Kotter, R. Motifs in brain networks. PLoS Biol. 2, e369 (2004).
98. Sakata, S., Komatsu, Y. & Yamamori, T. Local design principles of mammalian cortical networks. Neurosci. Res. 51, 309-315 (2005).
99. Song, S., Sjostrom, P. J., Reigl, M., Nelson, S. & Chklovskii, D. B. Highly nonrandom features of synaptic connectivity in local cortical circuits. PLoS Biol. 3, e68 (2005).
100. Alon, U. Biological networks: the tinkerer as an engineer. Science 301, 1866-1867 (2003).