@article {3140,
	title = {Characterizing the interplay between multiple levels of organization within bacterial sigma factor regulatory networks.},
	journal = {Nat Commun},
	volume = {4},
	year = {2013},
	month = {2013},
	pages = {1755},
	abstract = {<p>Bacteria contain multiple sigma factors, each targeting diverse, but often overlapping sets of promoters, thereby forming a complex network. The layout and deployment of such a sigma factor network directly impacts global transcriptional regulation and ultimately dictates the phenotype. Here we integrate multi-omic data sets to determine the topology, the operational, and functional states of the sigma factor network in Geobacter sulfurreducens, revealing a unique network topology of interacting sigma factors. Analysis of the operational state of the sigma factor network shows a highly modular structure with σ(N) being the major regulator of energy metabolism. Surprisingly, the functional state of the network during the two most divergent growth conditions is nearly static, with sigma factor binding profiles almost invariant to environmental stimuli. This first comprehensive elucidation of the interplay between different levels of the sigma factor network organization is fundamental to characterize transcriptional regulatory mechanisms in bacteria.</p>},
	keywords = {Energy Metabolism, Gene Expression Profiling, Gene Expression Regulation, Bacterial, Gene Regulatory Networks, Genes, Bacterial, Geobacter, Models, Biological, Regulon, Sigma Factor},
	issn = {2041-1723},
	doi = {10.1038/ncomms2743},
	author = {Qiu, Yu and Nagarajan, Harish and Embree, Mallory and Shieu, Wendy and Abate, Elisa and Ju{\'a}rez, Katy and Cho, Byung-Kwan and Elkins, James G and Nevin, Kelly P and Barrett, Christian L and Lovley, Derek R and Palsson, Bernhard O and Zengler, Karsten}
}
@article {436,
	title = {Genome-wide survey for PilR recognition sites of the metal-reducing prokaryote Geobacter sulfurreducens.},
	journal = {Gene},
	volume = {469},
	year = {2010},
	month = {2010 Dec 1},
	pages = {31-44},
	abstract = {Geobacter sulfurreducens is a species from the bacterial family Geobacteraceae, members of which participate in bioenergy production and in environmental bioremediation. G. sulfurreducens pili are electrically conductive and are required for Fe(III) oxide reduction and for optimal current production in microbial fuel cells. PilR is an enhancer binding protein, which is an activator acting together with the alternative sigma factor, RpoN, in transcriptional regulation. Both RpoN and PilR are involved in regulation of expression of the pilA gene, whose product is pilin, a structural component of a pilus. Using bioinformatic approaches, we predicted G. sulfurreducens sequence elements that are likely to be regulated by PilR. The functional importance of the genome region containing a PilR binding site predicted upstream of the pilA gene was experimentally validated. The predicted G. sulfurreducens PilR binding sites are similar to PilR binding sites of Pseudomonas and Moraxella. While the number of predicted PilR-regulated sites did not deviate from that expected by chance, multiple sites were predicted upstream of genes with roles in biosynthesis and function of pili and flagella, in secretory pathways, and in cell wall biogenesis, suggesting the possible involvement of G. sulfurreducens PilR in regulation of production and assembly of pili and flagella.},
	keywords = {Bacterial Proteins, Base Sequence, Binding Sites, Conserved Sequence, Ferric Compounds, Fimbriae Proteins, Gene Expression Regulation, Bacterial, Genome, Bacterial, Geobacter, Molecular Sequence Data, Promoter Regions, Genetic, Transcription Factors, Transcription, Genetic},
	issn = {1879-0038},
	doi = {10.1016/j.gene.2010.08.005},
	author = {Krushkal, Julia and Ju{\'a}rez, Katy and Barbe, Jose F and Qu, Yanhua and Andrade, Angel and Puljic, Marko and Adkins, Ronald M and Lovley, Derek R and Ueki, Toshiyuki}
}
@article {458,
	title = {Genome-wide analysis of the RpoN regulon in Geobacter sulfurreducens.},
	journal = {BMC Genomics},
	volume = {10},
	year = {2009},
	month = {2009},
	pages = {331},
	abstract = {BACKGROUND: The role of the RNA polymerase sigma factor RpoN in regulation of gene expression in Geobacter sulfurreducens was investigated to better understand transcriptional regulatory networks as part of an effort to develop regulatory modules for genome-scale in silico models, which can predict the physiological responses of Geobacter species during groundwater bioremediation or electricity production.

RESULTS: An rpoN deletion mutant could not be obtained under all conditions tested. In order to investigate the regulon of the G. sulfurreducens RpoN, an RpoN over-expression strain was made in which an extra copy of the rpoN gene was under the control of a taclac promoter. Combining both the microarray transcriptome analysis and the computational prediction revealed that the G. sulfurreducens RpoN controls genes involved in a wide range of cellular functions. Most importantly, RpoN controls the expression of the dcuB gene encoding the fumarate/succinate exchanger, which is essential for cell growth with fumarate as the terminal electron acceptor in G. sulfurreducens. RpoN also controls genes, which encode enzymes for both pathways of ammonia assimilation that is predicted to be essential under all growth conditions in G. sulfurreducens. Other genes that were identified as part of the RpoN regulon using either the computational prediction or the microarray transcriptome analysis included genes involved in flagella biosynthesis, pili biosynthesis and genes involved in central metabolism enzymes and cytochromes involved in extracellular electron transfer to Fe(III), which are known to be important for growth in subsurface environment or electricity production in microbial fuel cells. The consensus sequence for the predicted RpoN-regulated promoter elements is TTGGCACGGTTTTTGCT.

CONCLUSION: The G. sulfurreducens RpoN is an essential sigma factor and a global regulator involved in a complex transcriptional network controlling a variety of cellular processes.},
	keywords = {Bacterial Proteins, DNA, Bacterial, Gene Expression Profiling, Gene Expression Regulation, Bacterial, Genome-Wide Association Study, Geobacter, Multigene Family, Oligonucleotide Array Sequence Analysis, Promoter Regions, Genetic, Regulon, RNA Polymerase Sigma 54},
	issn = {1471-2164},
	doi = {10.1186/1471-2164-10-331},
	author = {Leang, Ching and Krushkal, Julia and Ueki, Toshiyuki and Puljic, Marko and Sun, Jun and Ju{\'a}rez, Katy and N{\'u}{\~n}ez, Cinthia and Reguera, Gemma and DiDonato, Raymond and Postier, Bradley and Adkins, Ronald M and Lovley, Derek R}
}
@article {490,
	title = {PilR, a transcriptional regulator for pilin and other genes required for Fe(III) reduction in Geobacter sulfurreducens.},
	journal = {J Mol Microbiol Biotechnol},
	volume = {16},
	year = {2009},
	month = {2009},
	pages = {146-58},
	abstract = {Growth using Fe(III) as a terminal electron acceptor is a critical physiological process in Geobacter sulfurreducens. However, the mechanisms of electron transfer during Fe(III) reduction are only now being understood. It has been demonstrated that the pili in G. sulfurreducens function as microbial nanowires conducting electrons onto Fe(III) oxides. A number of c-type cytochromes have also been shown to play important roles in Fe(III) reduction. However, the regulatory networks controlling the expression of the genes involved in such processes are not well known. Here we report that the expression of pilA, which encodes the pilistructural protein, is directly regulated by a two-component regulatory system in which PilR functions as an RpoN-dependent enhancer binding protein. Surprisingly, a deletion of the pilR gene affected not only insoluble Fe(III) reduction, which requires pili, but also soluble Fe(III) reduction, which, in contrast, does not require pili. Gene expression profiling using whole-genome DNA microarray and quantitative RT-PCR analyses obtained with a PilR-deficient mutant revealed that the expression of pilA and other pilin-related genes are downregulated, while many c-type cytochromes involved in Fe(III) reduction were differentially regulated. This is the first instance of an enhancer binding protein implicated in regulating genes involved in Fe(III) respiratory functions.},
	keywords = {Bacterial Proteins, Ferric Compounds, Fimbriae Proteins, Gene Expression Regulation, Bacterial, Genes, Regulator, Geobacter, Oxidation-Reduction, Transcription, Genetic},
	issn = {1660-2412},
	doi = {10.1159/000115849},
	author = {Ju{\'a}rez, Katy and Kim, Byoung-Chan and Nevin, Kelly and Olvera, Leticia and Reguera, Gemma and Lovley, Derek R and Meth{\'e}, Barbara A}
}
@article {489,
	title = {Computational and experimental analysis of redundancy in the central metabolism of Geobacter sulfurreducens.},
	journal = {PLoS Comput Biol},
	volume = {4},
	year = {2008},
	month = {2008 Feb},
	pages = {e36},
	abstract = {Previous model-based analysis of the metabolic network of Geobacter sulfurreducens suggested the existence of several redundant pathways. Here, we identified eight sets of redundant pathways that included redundancy for the assimilation of acetate, and for the conversion of pyruvate into acetyl-CoA. These equivalent pathways and two other sub-optimal pathways were studied using 5 single-gene deletion mutants in those pathways for the evaluation of the predictive capacity of the model. The growth phenotypes of these mutants were studied under 12 different conditions of electron donor and acceptor availability. The comparison of the model predictions with the resulting experimental phenotypes indicated that pyruvate ferredoxin oxidoreductase is the only activity able to convert pyruvate into acetyl-CoA. However, the results and the modeling showed that the two acetate activation pathways present are not only active, but needed due to the additional role of the acetyl-CoA transferase in the TCA cycle, probably reflecting the adaptation of these bacteria to acetate utilization. In other cases, the data reconciliation suggested additional capacity constraints that were confirmed with biochemical assays. The results demonstrate the need to experimentally verify the activity of key enzymes when developing in silico models of microbial physiology based on sequence-based reconstruction of metabolic networks.},
	keywords = {Bacterial Proteins, Base Sequence, Computer Simulation, Gene Expression Regulation, Bacterial, Geobacter, Models, Biological, Molecular Sequence Data, Multienzyme Complexes, Signal Transduction},
	issn = {1553-7358},
	doi = {10.1371/journal.pcbi.0040036},
	author = {Segura, Daniel and Mahadevan, Radhakrishnan and Ju{\'a}rez, Katy and Lovley, Derek R}
}
