Chapter 7 Genomic Approaches to Reconstructing Transcriptional Networks
Stephen J. W. Busby and Stephen D. Minchin
The traditional methods for discovering transcriptional regulatory networks in bacteria, based on genetics and biochemistry, are now being replaced by high throughput pan-genome methods. Experimental approaches include methods involving RNA or methods based on the direct observation of transcription factors. This chapter places the new methods in context and discusses their potential benefits and drawbacks.
Chapter 8 Structure and Evolution of Transcriptional Regulatory Networks
Guilhem Chalancon and M. Madan Babu
Regulation of gene expression is primarily mediated by proteins called transcription factors (TFs), which recognize and bind specific nucleotide sequences and affect transcription of nearby genes. Over the last years, considerable information has been accumulated on regulatory interactions between the TFs and their regulated target genes (TGs) in various model prokaryotic systems such as Escherichia coli and Bacillus subtilis. This has permitted researchers to model the transcriptional regulatory system of an organism as a network, wherein TFs or TGs are represented as nodes and regulatory interactions are denoted as directed links. Representation of this information as a network has provided us with a robust conceptual framework to investigate this system, and work in the last decade has uncovered several fundamental general principles pertaining to its structure and evolution. In this chapter, we first introduce the concept of transcriptional regulatory networks. We then discuss our current understanding of the structure of transcriptional regulatory networks. Specifically, we discuss the local and global structure of such networks. We then discuss the various forces that influence network evolution such as gene duplication, horizontal gene transfer, and gene loss. In particular, we discuss how the transcriptional regulatory network evolves across organisms that live in different environments. Finally, we conclude by discussing major challenges for future research and highlighting how the new understanding can have implications for biotechnology and medicine and can be exploited in applications such as microbial engineering and synthetic biology.
Chapter 9 Operation of the Gene Regulatory Network in Escherichia coli
Agustino Martínez-Antonio
Transcription factors function as sensory systems acting at the core of genetic regulatory switches. The transcriptional regulatory network in Escherichia coli can be studied as the integration of the whole of these genetic sensory systems. The operation of this regulatory system affect the expression of genes by interacting with the DNA at the promoter regions of transcription units. In this chapter I present the advances of what we know about the mechanistic logic for the operation of the regulatory program in E. coli. It is proposed that for a better understanding on the operation of the regulatory network it should be considered the globalism of transcription factors, the signal perceived by each, their co-regulating activity, the genome position of regulatory and target genes, and cellular concentration of the regulatory proteins, among others.
Chapter 10 Bacillus subtilis Transcriptional Network
Yuko Makita and Kenta Nakai
Bacillus subtilis is a soil living bacterium, long known as a representative of the low G+C group of Gram-positive bacteria in contrast to Escherichia coli, a representative of Gram-negative bacteria. Its genome contains about 4,176 protein-coding genes and 178 RNA genes. The number of sigma factors is 18, which is much larger than 7 in E. coli. Although there are very few theoretical studies of its global transcriptional network, our preliminary analysis based on experimentally validated data stored in the DBTBS database suggests that it is a typical scale-free network largely governed by a small number of hub transcription factors like that of many other model organisms. However, some of the results of the network motif analysis in E. coli were not confirmed in B. subtilis. Although this is likely to be due to the small sample size in B. subtilis, a more cautious approach might be necessary to perform network motif analyses of bacterial gene regulatory networks, which are not so large, in general. As a specific sub-network, the gene regulatory network for sporulation, which is regarded as a model of eukaryotic differentiation process, is described. In the description of the network, not only transcriptional regulation but also post-translational regulation as well as genome recombination are necessary.
Chapter 11 Helicobacter pylori Transcriptional Network
Alberto Danielli and Vincenzo Scarlato
The human gastric pathogen Helicobacter pylori appears to enroll only 17 transcriptional regulators to transduce environmental signals into coordinated output expression of the genome. We show that the low number of transcriptional regulators, together with the large body of molecular tools, set H. pylori as appealing model organism to characterize transcriptional network structures involved in virulence regulation and host-pathogen interactions. In particular we provide evidence that the regulators are wired in a shallow transcriptional regulatory network (TRN), which orchestrates the key physiological responses needed to colonize the gastric niche: heat and stress response, motility and chemotaxis, acid acclimation and metal ion homeostasis. Interestingly, long regulatory cascades are absent, and rather than having a plethora of specialized regulators, the TRN of H. pylori appears to transduce separate environmental inputs by using different combinations of a small set of regulators. It is not tailored to adapt to many environmental stimuli, and apparently not flexible to react to metabolic signals encountered outside of the gastric niche. On the other hand, the predominance of negative regulatory interactions suggests that this architecture of the TRN evolved to quickly respond to changing conditions in the gastric niche in order to maintain homeostasis. Metal-responsive regulators such as NikR and Fur appear to have a very important role in this TRN, forming a central regulatory hub, with regulatory interaction feeding into all other sub-network circuits.
Chapter 12 The Transcriptional Regulatory Network of Mycobacterium tuberculosis
Gábor Balázsi, Oleg A. Igoshin, and Maria Laura Gennaro
Approximately one third of the worldâ |
发表于 2013-6-8 10:17
