Nature Genetics
31, 64 - 68 (2002)
Published online: 22 April 2002; | doi:10.1038/ng881
Network motifs in the transcriptional regulation network of Escherichia coliShai S. Shen-Orr1, Ron Milo2, Shmoolik Mangan1
& Uri Alon1, 21
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. 2
Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel.
Correspondence should be addressed to Uri Alon urialon@wisemail.weizmann.ac.ilLittle is known about the design principles1,
2,
3,
4,
5,
6,
7,
8,
9,
10 of transcriptional regulation networks that control gene expression in cells. Recent advances in data collection and analysis2,
11,
12, however, are generating unprecedented amounts of information about gene regulation networks. To understand these complex wiring diagrams1,
2,
3,
4,
5,
6,
7,
8,
9,
10,
13, we sought to break down such networks into basic building blocks2. We generalize the notion of motifs, widely used for sequence analysis, to the level of networks. We define 'network motifs' as patterns of interconnections that recur in many different parts of a network at frequencies much higher than those found in randomized networks. We applied new algorithms for systematically detecting network motifs to one of the best-characterized regulation networks, that of direct transcriptional interactions in Escherichia coli
3,
6. We find that much of the network is composed of repeated appearances of three highly significant motifs. Each network motif has a specific function in determining gene expression, such as generating temporal expression programs and governing the responses to fluctuating external signals. The motif structure also allows an easily interpretable view of the entire known transcriptional network of the organism. This approach may help define the basic computational elements of other biological networks.
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