An extended transcriptional regulatory network of Escherichia coli and analysis of its hierarchical structure and network motifs.

Recent studies of genome-wide transcriptional regulatory network (TRN) revealed several intriguing structural and dynamic features of gene expression at a system level. Unfortunately, the network under study is often far from complete. A critical question is thus how much the network is incomplete and to what extent this would affect the results of analysis. Here we compare the Escherichia coli TRN built by Shen-Orr et al. (Nature Genet., 31, 64-68) with two TRNs reconstructed from RegulonDB and Ecocyc respectively and present an extended E.coli TRN by integrating information from these databases and literature. The scale of the extended TRN is about twice as large as the previous ones. The new network preserves the multi-layer hierarchical structure which we recently reported but has more layers. More global regulators are inferred. While the feed forward loop (FFL) is confirmed to be highly representative in the network, the distribution of the different types of FFLs is different from that based on the incomplete network. In contrast to the notion of motif aggregation and formation of homologous motif clusters, we found that most FFLs interact and form a giant motif cluster. Furthermore, we show that only a small portion of the genes is solely regulated by only one FFL. Many genes are regulated by two or more interacting FFLs or other more complicated network motifs together with transcriptional factors not belonging to any network motifs, thereby forming complex regulatory circuits. Overall, the extended TRN represents a more solid basis for structural and functional analysis of genome-wide gene regulation in E.coli.

[1]  N. W. Davis,et al.  The complete genome sequence of Escherichia coli K-12. , 1997, Science.

[2]  Kenneth E. Rudd,et al.  EcoGene: a genome sequence database for Escherichia coli K-12 , 2000, Nucleic Acids Res..

[3]  S. Shen-Orr,et al.  Networks Network Motifs : Simple Building Blocks of Complex , 2002 .

[4]  P. Bourgine,et al.  Topological and causal structure of the yeast transcriptional regulatory network , 2002, Nature Genetics.

[5]  S. Shen-Orr,et al.  Network motifs in the transcriptional regulation network of Escherichia coli , 2002, Nature Genetics.

[6]  Yaniv Ziv,et al.  Revealing modular organization in the yeast transcriptional network , 2002, Nature Genetics.

[7]  Nicola J. Rinaldi,et al.  Transcriptional Regulatory Networks in Saccharomyces cerevisiae , 2002, Science.

[8]  S. Shen-Orr,et al.  Network motifs: simple building blocks of complex networks. , 2002, Science.

[9]  Peter D. Karp,et al.  The EcoCyc Database , 2002, Nucleic Acids Res..

[10]  S. Gottesman,et al.  A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[11]  George M Church,et al.  Regulatory network of acid resistance genes in Escherichia coli , 2003, Molecular microbiology.

[12]  S. Mangan,et al.  Structure and function of the feed-forward loop network motif , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[13]  An-Ping Zeng,et al.  Reconstruction of metabolic networks from genome data and analysis of their global structure for various organisms , 2003, Bioinform..

[14]  Alexander E. Kel,et al.  TRANSFAC®: transcriptional regulation, from patterns to profiles , 2003, Nucleic Acids Res..

[15]  Markus J. Herrgård,et al.  Reconciling gene expression data with known genome-scale regulatory network structures. , 2003, Genome research.

[16]  J. Collado-Vides,et al.  Identifying global regulators in transcriptional regulatory networks in bacteria. , 2003, Current opinion in microbiology.

[17]  Nicola J. Rinaldi,et al.  Computational discovery of gene modules and regulatory networks , 2003, Nature Biotechnology.

[18]  Araceli M. Huerta,et al.  Regulatory network of Escherichia coli: consistency between literature knowledge and microarray profiles. , 2003, Genome research.

[19]  S. Mangan,et al.  The coherent feedforward loop serves as a sign-sensitive delay element in transcription networks. , 2003, Journal of molecular biology.

[20]  Albert-László Barabási,et al.  Aggregation of topological motifs in the Escherichia coli transcriptional regulatory network , 2004, BMC Bioinformatics.

[21]  D. Pe’er,et al.  Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data , 2003, Nature Genetics.

[22]  M. Gerstein,et al.  Genomic analysis of gene expression relationships in transcriptional regulatory networks. , 2003, Trends in genetics : TIG.

[23]  A. Arkin,et al.  Motifs, modules and games in bacteria. , 2003, Current opinion in microbiology.

[24]  S. Teichmann,et al.  Evolution of transcription factors and the gene regulatory network in Escherichia coli. , 2003, Nucleic acids research.

[25]  E. Nimwegen.  Scaling Laws in the Functional Content of Genomes , 2003, physics/0307001.

[26]  M. Gerstein,et al.  Structure and evolution of transcriptional regulatory networks. , 2004, Current opinion in structural biology.

[27]  W. Wasserman,et al.  Regulog analysis: detection of conserved regulatory networks across bacteria: application to Staphylococcus aureus. , 2004, Genome research.

[28]  Markus J Herrgård,et al.  Flagellar Biosynthesis In Silico Building Quantitative Models of Regulatory Networks , 2004, Cell.

[29]  Markus J. Herrgård,et al.  Reconstruction of microbial transcriptional regulatory networks. , 2004, Current opinion in biotechnology.

[30]  Uri Alon,et al.  Efficient sampling algorithm for estimating subgraph concentrations and detecting network motifs , 2004, Bioinform..

[31]  Katy C. Kao,et al.  Transcriptome-based determination of multiple transcription regulator activities in Escherichia coli by using network component analysis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[32]  An-Ping Zeng,et al.  Hierarchical structure and modules in the Escherichia coli transcriptional regulatory network revealed by a new top-down approach , 2004, BMC Bioinformatics.

[33]  Daniel W. A. Buchan,et al.  Evolution of protein superfamilies and bacterial genome size. , 2004, Journal of molecular biology.

[34]  M. Gerstein,et al.  Annotation transfer between genomes: protein-protein interologs and protein-DNA regulogs. , 2004, Genome research.

[35]  M. Wall,et al.  Design of gene circuits: lessons from bacteria , 2004, Nature Reviews Genetics.

[36]  Julio Collado-Vides,et al.  RegulonDB (version 4.0): transcriptional regulation, operon organization and growth conditions in Escherichia coli K-12 , 2004, Nucleic Acids Res..

[37]  S. Gottesman.  The small RNA regulators of Escherichia coli: roles and mechanisms*. , 2004, Annual review of microbiology.

[38]  H. Fromm,et al.  GABA in plants: just a metabolite? , 2004, Trends in plant science.

[39]  M. Gerstein,et al.  Genomic analysis of regulatory network dynamics reveals large topological changes , 2004, Nature.