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PubMed2004

Characterization of the maize endosperm transcriptome and its comparison to the rice genome.

The cereal endosperm is a major organ of the seed and an important component of the world's food supply. To understand the development and physiology of the endosperm of cereal seeds, we focused on the identification of genes expressed at various times during maize endosperm development. We constructed several cDNA libraries to identify full-length clones and subjected them to a twofold enrichment. A total of 23,348 high-quality sequence-reads from 5'- and 3'-ends of cDNAs were generated and assembled into a unigene set representing 5326 genes with paired sequence-reads. Additional sequencing yielded a total of 3160 (59%) completely sequenced, full-length cDNAs. From 5326 unigenes, 4139 (78%) can be aligned with 5367 predicted rice genes and by taking only the "best hit" be mapped to 3108 positions on the rice genome. The 22% unigenes not present in rice indicate a rapid change of gene content between rice and maize in only 50 million years. Differences in rice and maize gene numbers also suggest that maize has lost a large number of duplicated genes following tetraploidization. The larger number of gene copies in rice suggests that as many as 30% of its genes arose from gene amplification, which would extrapolate to a significant proportion of the estimated 44,027 candidate genes of its entire genome. Functional classification of the maize endosperm unigene set indicated that more than a fourth of the novel functionally assignable genes found in this study are involved in carbohydrate metabolism, consistent with its role as a storage organ.

DNA, Complementary↗

PubMed2003

The auxin-induced transcriptome for etiolated Arabidopsis seedlings using a structure/function approach.

To increase our understanding of the mode of action of auxin, we analyzed auxin-induced changes in the Arabidopsis transcriptome with microarrays representing 20426 Arabidopsis genes. Treatment of etiolated seedlings with low concentrations of the auxin, indole-3-acetic acid (IAA), decreased the expression levels of 23 genes, whereas it increased the expression levels of 47 genes within 20 min. After 40 min, the directional trend in genomic change was predominantly an increase in gene expression. Among the most rapidly induced changes are those in genes encoding transcription factors. Promoter regions of transiently induced genes contained DNA motifs that bind auxin response (ARFAT) and silence element binding factors whereas genes induced by IAA during the entire experimental period contained MYC and ARFAT DNA motifs at higher frequencies. Six structurally diverse auxins were analyzed to determine genes that are unique to a specific auxin, as well as a common set of genes that are rapidly regulated by all tested auxins, thus enabling the identification of shared DNA motifs. In addition to ARFAT, analysis of promoter regions of genes induced by all six auxins revealed the presence of an abscisic-acid-responsive DC3 promoter-binding factor and low temperature responsive elements suggesting a possible role for abscisic acid in modulating auxin-induced responses.

5' Untranslated Regions↗

PubMed2004

Detection of novel splice forms in human and mouse using cross-species approach.

Millions of transcript sequences have become available for characterizing the transcriptome of human and mouse. Transcript databases have been extensively mined for extracting alternative splicing information within the same species; but they also represent a potentially valuable resource for the discovery of alternative splice variants in another species. In this study, we have performed analysis of alternative splicing patterns for 7,475 pairs of human and mouse genes. We found that cross-species transcript analysis could accomplish the same level of sensitivity in detecting constitutive splice patterns as EST resource from the same species. In contrast, identifying alternative splice patterns in human genes, mouse transcripts achieved only 50% of the sensitivity of human EST and 70% of the sensitivity of human mRNA. While identifying alternative splice patterns in mouse genes, human transcripts are 38% more sensitive than mouse mRNA, and reach 60% of the sensitivity of mouse EST. Furthermore, using the cross-species approach, we predicted novel alternative splice patterns for 42% of human genes and 51% of mouse genes. Splice site motif analysis suggests that the majority of predicted novel splice patterns are expressed in human. EST-based frequency analysis shows that novel splice patterns are expressed at lower frequency than alternative splice patterns present in the transcript data from both species, possibly explaining why they remain undetected in the transcript data of the same species.

Alternative Splicing↗

PubMed2004

Global analysis of nutrient control of gene expression in Saccharomyces cerevisiae during growth and starvation.

Global gene expression in yeast was examined in five different nutrient-limited steady states and in their corresponding starvation-induced stationary phases. The use of chemostats, with their ability to generate defined and reproducible physiological conditions, permitted the exclusion of the confounding variables that frequently complicate transcriptome analyses. This approach allowed us to dissect out effects on gene expression that are specific to particular physiological states. Thus, we discovered that a large number of ORFs involved in protein synthesis were activated under ammonium limitation, whereas the expression of ORFs concerned with energy and metabolism was enhanced by carbon limitation. Elevated transcription of genes in high-affinity glucose uptake, the trichloroacetic acid cycle, and oxidative phosphorylation were observed in glucose-limiting, but not glucose-abundant, conditions. In contrast, genes involved in gluconeogenesis and, interestingly, genes subject to nitrogen catabolite repression increased their transcription when ethanol was the carbon source, even though ammonium was in excess. This result suggests that up-regulation of genes sensitive to nitrogen catabolite repression may contribute anapleurotic intermediates in ethanol-grown cells. The different starvation conditions produced two general types of transcription profiles, with carbon-starved cells transcribing far fewer genes than cells starved for any of the other macronutrients. Nonetheless, each starvation condition induced its own peculiar set of genes, and only 17 genes were induced >5-fold by all five starvations. In all cases, analysis of the upstream sequences of clusters of coregulated genes identified motifs that may be recognized by transcription factors specific for controlling gene expression in each of the physiological conditions examined.

Cell Division↗

PubMed2006

Comprehensive genome and transcriptome analysis of the 11q13 amplicon in human oral cancer and synteny to the 7F5 amplicon in murine oral carcinoma.

11q13 amplification occurs in a wide variety of tumors, including almost half of oral squamous cell carcinomas (OSCC) where it has been correlated with a poor outcome. In this study, we compiled 3.6 Mb of DNA sequence in the 11q13 amplicon core and refined the physical map of the amplicon. In the process, we determined the genomic structure and normal tissue expression patterns of two recently identified genes, TAOS2/TMEM16A and MRGF, which reside in the amplicon core. We then quantified DNA copy number and mRNA expression of all genes in the 11q13 amplicon in cell lines and primary tumors from OSCC. With the exception of FGF3, FGF4, FGF19, and MRGF, all genes were overexpressed in most tumors with genomic amplification. Furthermore, we found that the expression of genes in the amplicon appeared to be highly coordinated, making it difficult to determine which gene or genes are driving amplification. However, in nonamplified primary tumors, three genes, TAOS2/TMEM16A, OCIM, and TPCN2, are frequently overexpressed, whereas CCND1 and EMS1 are not. These results suggest that in addition to CCND1 and EMS1, other important genes also may be target genes driving 11q13 amplification. We hypothesize that 11q13 amplification may be driven by a cassette of genes that provide growth or metastatic advantage to cancer cells. This is supported by the finding that the human 11q13 amplicon core is syntenic to mouse chromosomal band 7F5, which is frequently amplified in chemically induced murine OSCC. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat

Animals↗

PubMed2005

Transcriptional changes underlying the secretory activation phase of mammary gland development.

The secretory activation stage of mammary gland development occurs after parturition and converts inactive lobuloalveoli to active milk secretion. This process is triggered by progestin withdrawal and depends upon augmented prolactin (Prl) signaling. Little is known about the Prl-induced transcriptional changes that occur in the mammary gland to drive this process. To examine changes in the mammary transcriptome responsible for secretory activation, we have used transcript profiling of three mouse models that exhibit failure of secretory activation: knockout of galanin (a regulator of pituitary Prl production and a mammary cell autonomous modulator of Prl action); treatment with S179D Prl (a phosphoprolactin mimic); and knockout of a single Prl receptor allele. A significant reduction in expression was observed in genes belonging to 46 gene ontologies including those representing milk proteins, metabolism, lipid, cholesterol and fatty acid biosynthetic enzymes, immune response, and key transcription factors. A set of 35 genes, commonly regulated in all three models, was identified and their role in lactogenesis was validated by examining their expression in response to Prl stimulation or signal transducer and activator of transcription 5 knockdown in the HC11 mouse mammary cell culture model. The transcript profiles provided by these experiments identify 35 key genes (many for the first time) involved in the secretory activation phase of mammary gland development, show that S179D acts as an antagonist of Prl action, and provide insight into the partial penetrance of failed lactation in Prl receptor heterozygous females.

Alleles↗

PubMed2003

Transcriptome analysis of sulfur depletion in Arabidopsis thaliana: interlacing of biosynthetic pathways provides response specificity.

Higher plants assimilate inorganic sulfate into cysteine, which is subsequently converted to methionine, and into a variety of other sulfur-containing organic compounds. To resist sulfur deficiency, plants must demonstrate physiological flexibility: the expression of an extensive set of genes and gene regulators that act in the affected pathways or signalling cascades must be delicately tuned in response to environmental challenges. To elucidate this network of interactions, we have applied an array hybridisation/transcript profiling method to Arabidopsis plants subjected to 6, 10 and 13 days of constitutive and induced sulfur starvation. The temporal expression behaviour of approximately 7200 non-redundant genes was analysed simultaneously. The experiment was designed in a way to identify statistically significant changes of gene expression based on sufficient numbers of repeated hybridisations performed with five uniform pools of plant material. The expression profiles were processed to select differentially expressed genes. Among the 1507 sulfur-responsive clones implicated in this way, 632 genes responded specifically to sulfur deficiency by significant over-expression. The sulfur-responsive genes were grouped according to functional categories or biosynthetic pathways. As expected, genes of the sulfur assimilation pathway were altered in expression. Furthermore, genes involved in flavonoid, auxin, and jasmonate biosynthesis pathways were upregulated in conditions of sulfur deficiency. Based on the correlative analysis of gene expression patterns, we suggest that a complex co-ordination of systematic responses to sulfur depletion is provided via integration of flavonoid, auxin and jasmonate pathway elements. Plait concept for transduction of specificity via the main non-specific signalling stream is proposed.

Adaptation, Physiological↗

PubMed2005

Applying metabolic profiling techniques for stimulus-response experiments: chances and pitfalls.

So far it is mainly transcriptome and proteome analysis that has been applied to elucidate the correlation between genotype and phenotype although thorough metabolome studies can provide substantial information on the control of the metabolism at the biochemical level. Stimulus-response experiments, i.e. the investigation of metabolism dynamics after a glucose pulse (pulse experiment), can be used to study the in vivo enzyme kinetics offering insight into underlying reaction mechanisms. Usually, this requires rapid cell quenching combined with cell inactivation to'freeze' the microbial metabolism response at a definite time-lag after pulse stimulation. To access the 'frozen' metabolic reply, adequate analytical methods are needed to measure intracellular metabolite concentrations in the cell extract. As shown in the introductory review part, stimulus-response experiments were usually applied to study central metabolism dynamics in wildtype strains. Our own results, presented in the second part of the contribution, indicate that stimulus-response experiments should also be applied to analyse pathway dynamics in anabolic routes. Using the example of the aromatic amino acid pathway, an LC-MS/MS technique is presented that allows the quantification of intracellular pools of central metabolism as well as of the aromatic amino acid pathway. Based on the analytical approach metabolic profiling is performed to monitor the metabolism dynamics after a glucose pulse experiment allowing the conclusion that pulse stimulation is transmitted to the anabolic pathway of interest.

Algorithms↗

PubMed2004

An insight into the salivary transcriptome and proteome of the adult female mosquito Culex pipiens quinquefasciatus.

To obtain an insight into the salivary transcriptome and proteome (sialome) of the adult female mosquito Culex quinquefasciatus, a cDNA library was randomly sequenced, and aminoterminal information for selected proteins and peptides was obtained. cDNA sequence clusters coding for secreted proteins were further analyzed. The transcriptome revealed messages coding for several proteins of known families previously reported in the salivary glands of other blood-feeding insects as well as immune-related products such as C-type lectin, gambicin, and members of the prophenol oxidase cascade. Additionally, several transcripts coding for low-complexity proteins were found, some clearly coding for mucins. Many novel transcripts were found, including a novel endonuclease previously described in crabs and shrimps but not in insects; a hyaluronidase, not described before in mosquito salivary glands but found in venom glands and in salivary glands of sand flies and black flies; several cysteine-rich peptides with possible anticlotting function, including one similar to a previously described nematode family of anti-proteases; and a completely novel family of cysteine- and tryptophane-rich proteins (CWRC family) for which 12 full-length sequences are described. Also described are 14 additional novel proteins and peptides whose function and/or family affiliation are unknown. In total, 54 transcripts coding for full-length proteins are described. That several of these are translated into proteins was confirmed by finding the corresponding aminoterminal sequences in the SDS-PAGE/Edman degradation experiments. Electronic versions of all tables and sequences can be found at http://www.ncbi.nlm.nih.gov/projects/Mosquito/C_quinquefasciatus_sialome.

Amino Acid Sequence↗

PubMed2026

The novel transcriptional activator Bhr1 combining NTPase and Zn(II)2Cys6 DNA-binding domains controls (hemi-)cellulase response to mannose-rich substrates in the white-rot fungus Dichomitus squalens.

The regulatory landscape responsible for lignocellulose degradation in white-rot basidiomycete fungi remains largely unexplored. In this study, we characterize a novel transcriptional activator, Bhr1, in the white-rot fungus Dichomitus squalens. Bhr1 exhibits an unusual domain architecture that combines a septin-like P-loop NTPase fold with Zn(II)2Cys6 DNA-binding domains and plays a critical role in activating (hemi-)cellulase enzyme production when D. squalens is exposed to mannose-rich substrates. Using CRISPR/Cas9-mediated gene editing, we generated a bhr1 disruption mutant that displayed distinct phenotypes and enzyme activity profiles on mannose and guar gum compared to the wild type. RNA sequencing data indicate that Bhr1 induces specific (hemi-)cellulase-encoding genes without altering the expression of genes encoding sugar transporters or sugar metabolic enzymes. Phylogenetic analyses show that Bhr1 is basidiomycete specific and largely restricted to saprotrophic and plant-associated Agaricomycetes fungi. Based on the domain architecture of Bhr1 and the effects of its disruption in D. squalens, our findings reveal a lineage-specific regulatory innovation in basidiomycetes that is distinct from those described in ascomycetes. Elucidating the function and evolutionary conservation of Bhr1 advances our understanding of lignocellulose degradation at the molecular level in basidiomycete fungi and may inform studies of their ecological adaptation and the development of biotechnological applications.IMPORTANCEUnderstanding the transcriptional regulatory mechanisms in white-rot fungi, such as Dichomitus squalens, is crucial for advancing our knowledge of lignocellulose degradation. This study identifies D. squalens Bhr1 as a key regulator of (hemi-)cellulase production on mannose-rich substrates and further distinguishes basidiomycete transcription factors involved in plant biomass degradation from their ascomycete counterparts. Our findings highlight the significance of lineage-specific regulators in facilitating adaptive enzyme production for efficient biomass utilization, which is critical to carbon cycling in terrestrial ecosystems. This work establishes a foundation for exploring novel regulatory strategies among wood-degrading fungi, potentially enabling targeted strain engineering in biotechnological applications.

Mannose↗

PubMed2002

Marked increase in CC chemokine gene expression in both human and mouse mast cell transcriptomes following Fcepsilon receptor I cross-linking: an interspecies comparison.

Rodent mast cells (MCs) are common experimental tools but are somewhat different from their human counterparts in their responses to certain cytokines and drugs. We examined the expression of more than 10 000 distinct genes in human and mouse cultured MCs using high-density oligonucleotide probe arrays to find molecules similarly regulated and expressed by the 2 MC types. After stimulation via high-affinity Fcepsilon receptor I (FcepsilonRI), the transcriptional levels of several CC chemokines were markedly increased, and I-309 (CCL1), macrophage inflammatory protein-1alpha (MIP-1alpha) (CCL3) and MIP-1beta (CCL4) were found among the 10 most increased human and mouse transcripts from approximately 12 000 genes (including some expressed sequence tags). In addition, a costimulatory molecule that was originally found on the membrane of activated T cells, 4-1BB (CD137), was found among the 10 most increased transcripts. The FcepsilonRI-induced expression of CC chemokines and 4-1BB was also detected at the protein level in both MC types. The conservation of these responses suggests that MCs play a crucial role in recruitment of various CCR-expressing cells into the tissue in a manner dependent on immunoglobin E, and that FcepsilonRI-mediated induction of several CC chemokines and 4-1BB is highly conserved between human and mouse. Interspecies comparison studies at the whole genome expression level should be useful for the interpretation of experimental data obtained in animal models of human pathobiology.

Animals↗

PubMed2007

IL-22 participates in an innate anti-HIV-1 host-resistance network through acute-phase protein induction.

Certain individuals are resistant to HIV-1 infection, despite repeated exposure to the virus. Although protection against HIV-1 infection in a small proportion of Caucasian individuals is associated with mutant alleles of the CCR5 HIV-1 coreceptor, the molecular mechanism underlying resistance in repeatedly HIV-1-exposed, uninfected individuals (EU) is unclear. In this study, we performed complementary transcriptome and proteome analyses on peripheral blood T cells, and plasma or serum from EU, their HIV-1-infected sexual partners, and healthy controls, all expressing wild-type CCR5. We report that activated T cells from EU overproduce several proteins involved in the innate immunity response, principally those including high levels of peroxiredoxin II, a NK-enhancing factor possessing strong anti-HIV activity, and IL-22, a cytokine involved in the production of acute-phase proteins such as the acute-phase serum amyloid A (A-SAA). Cell supernatants and serum levels of these proteins were up-regulated in EU. Moreover, a specific biomarker for EU detected in plasma was identified as an 8.6-kDa A-SAA cleavage product. Incubation of in vitro-generated myeloid immature dendritic cells with A-SAA resulted in CCR5 phosphorylation, down-regulation of CCR5 expression, and strongly decreased susceptibility of these cells to in vitro infection with a primary HIV-1 isolate. Taken together, these results suggest new correlates of EU protection and identify a cascade involving IL-22 and the acute phase protein pathway that is associated with innate host resistance to HIV infection.

Acute-Phase Proteins↗

PubMed2003

Relevance network between chemosensitivity and transcriptome in human hepatoma cells.

Generally, hepatoma is not a chemosensitive tumor, and the mechanism of resistance to anticancer drugs is not fully elucidated. We aimed to comprehensively evaluate the relationship between chemosensitivity and gene expression profile in human hepatoma cells, by using microarray analysis, and analyze the data by constructing relevance networks. In eight hepatoma cell lines (HLE, HLF, Huh7, Hep3B, PLC/PRF/5, SK-Hep1, Huh6, and HepG2), the baseline expression levels of 2300 genes were measured by cDNA microarray. The concentrations of eight anticancer drugs (nimustine, mitomycin C, cisplatin, carboplatin, doxorubicin, epirubicin, mitoxantrone, and 5-fluorouracil) needed for 50% growth inhibition were examined and used as a measure of chemosensitivity. These data were combined and comprehensive pair-wise correlations between gene expression levels and the 50% growth inhibition values were calculated. Significant correlations with significance were used to construct networks of similarity. Fifty-two relations, including 42 genes, were selected. Among them, nearly 20% were various types of transporters, and most of them negatively correlated with chemosensitivity. Transporter associated with antigen processing 1 was associated with resistance to mitoxantrone, consistent with previous reports. Other transporters were not reported previously to associate with chemosensitivity. Resistance to doxorubicin and its analogue, epirubicin, were positively correlated with topoisomerase II beta expression, whereas it negatively correlated with expression of carboxypeptidases A3 and Z. Response to nimustine was associated with expression of superoxide dismutase 2. Relevance networks identified several negative correlations between gene expression and resistance, which were missed by hierarchical clustering. Our results suggested the necessity of systematically evaluating the transporting systems that may play a major role in resistance in hepatoma. This may provide useful information to modify anticancer drug action in hepatoma.

Antineoplastic Agents↗

PubMed2004

Identification of "pathologs" (disease-related genes) from the RIKEN mouse cDNA dataset using human curation plus FACTS, a new biological information extraction system.

BACKGROUND: A major goal in the post-genomic era is to identify and characterise disease susceptibility genes and to apply this knowledge to disease prevention and treatment. Rodents and humans have remarkably similar genomes and share closely related biochemical, physiological and pathological pathways. In this work we utilised the latest information on the mouse transcriptome as revealed by the RIKEN FANTOM2 project to identify novel human disease-related candidate genes. We define a new term "patholog" to mean a homolog of a human disease-related gene encoding a product (transcript, anti-sense or protein) potentially relevant to disease. Rather than just focus on Mendelian inheritance, we applied the analysis to all potential pathologs regardless of their inheritance pattern. RESULTS: Bioinformatic analysis and human curation of 60,770 RIKEN full-length mouse cDNA clones produced 2,578 sequences that showed similarity (70-85% identity) to known human-disease genes. Using a newly developed biological information extraction and annotation tool (FACTS) in parallel with human expert analysis of 17,051 MEDLINE scientific abstracts we identified 182 novel potential pathologs. Of these, 36 were identified by computational tools only, 49 by human expert analysis only and 97 by both methods. These pathologs were related to neoplastic (53%), hereditary (24%), immunological (5%), cardio-vascular (4%), or other (14%), disorders. CONCLUSIONS: Large scale genome projects continue to produce a vast amount of data with potential application to the study of human disease. For this potential to be realised we need intelligent strategies for data categorisation and the ability to link sequence data with relevant literature. This paper demonstrates the power of combining human expert annotation with FACTS, a newly developed bioinformatics tool, to identify novel pathologs from within large-scale mouse transcript datasets.

Animals↗

PubMed2004

Study of Arabidopsis thaliana resistome in response to cucumber mosaic virus infection using whole genome microarray.

The plant innate immune response is mediated by resistance (R) genes and involves hypersensitive response (HR) cell death. During resistance responses, the host undergoes net changes in the transcriptome. To understand these changes, we generated a whole genome transcript profile for RCY1-mediated resistance to cucumber mosaic virus strain Y (CMV-Y) in Arabidopsis. Using a very stringent selection criterion, we identified 444 putative factors belonging to nine different functional classes that show significant transcript regulation during Arabidopsis-CMV-Y interaction. Genes with unknown function formed the largest class. Other functional classes represented in the resistome include kinases and phosphatases, protein degradation machinery/proteases, transcriptional regulators, and others. Interestingly, several of the unknown function genes possess well characterized domains and secondly many genes encode small peptides with less than 100 amino acids. Analysis of 1.1 kb promoter regions of the 444 genes revealed that 9 out of the 12 known cis-binding elements are significantly associated with pathogen responsive cluster. Location and distribution of five prominent binding elements for select group of disease resistance related and unknown function genes is presented. The analysis also revealed 80 defense-responsive genes that might participate in R gene-mediated defense against both viral and bacterial pathogens. In addition, chromosome distribution of genes that respond to bacterial and viral pathogens suggests that they are located in small gene clusters and may be transcriptionally co-regulated. Exploring the precise function of the new genes identified in this analysis will offer new insights into plant defense.

Analysis of Variance↗

PubMed2005

Hepatic to pancreatic switch defines a role for hemostatic factors in cellular plasticity in mice.

In multiple systems, impaired proteolysis associated with the loss of the hemostatic factor plasminogen (Plg) results in fibrin-dependent defects in tissue repair. However, repair within the liver is known to be defective in Plg-deficient (Plg(o)) mice independent of fibrin clearance and appears to be compromised in part by the poor clearance of necrotic cells. Based on these findings, we examined the hepatic transcriptome after injury in search of transcriptional programs that are sensitive to the Plg/fibrinogen system. To this end, we generated biotinylated cRNA pools from livers of Plg(o) mice and controls before and after a single dose of the hepatotoxin carbon tetrachloride and hybridized them against high-density oligonucleotide arrays. Analysis of the gene expression platform identified an unexpected transcriptional signature within challenged livers of Plg(o) mice for pancreatic gene products, including trypsinogen-2, amylase-2, elastase-1, elastase-2, and cholesteryl-ester lipase. Validation studies found that this transcriptional program also contained products of the endocrine pancreas (Reg-1 and insulin genes) and the expression of the pancreatic transcription factors p48 and PDX-1. By using a LacZ transgene to trace the cellular source of pancreatic gene expression, we found that PDX-1 was expressed in albumin-positive cells that were morphologically indistinguishable from hepatocytes, and in albumin-negative epithelioid cells within zones of pericentral injury. More detailed studies revealed that the mechanisms of heterotopic gene expression in Plg(o) mice required fibrin(ogen). Collectively, these data reveal a regulatory role for the hemostatic factors plasmin(ogen) and fibrin(ogen) in cellular plasticity within adult tissues of the digestive system.

Amylases↗

PubMed2005

Global expression profiling of Bacillus subtilis cells during industrial-close fed-batch fermentations with different nitrogen sources.

A detailed gene expression analysis of industrial-close Bacillus subtilis fed-batch fermentation processes with casamino acids as the only nitrogen source and with a reduced casamino acid concentration but supplemented by ammonia was carried out. Although glutamine and arginine are supposed to be the preferred nitrogen sources of B. subtilis, we demonstrate that a combined feeding of ammonia and casamino acids supports cell growth under fed-batch fermentation conditions. The transcriptome and proteome analyses revealed that the additional feeding of ammonia in combination with a reduced amino acid concentration results in a significantly lower expression level of the glnAR or tnrA genes, coding for proteins, which are mainly involved in the nitrogen metabolism of B. subtilis. However, the mRNA levels of the genes of the ilvBHC-leuABD and hom-thrCB operons were significantly increased, indicating a valine, leucine, isoleucine, and threonine limitation under these fermentation conditions. In contrast, during the fermentation with casamino acids as the only nitrogen source, several genes, which play a crucial role in nitrogen metabolism of B. subtilis (e.g., glnAR, nasCDE, nrgAB, and ureABC), were up-regulated, indicating a nitrogen limitation under these conditions. Furthermore, increased expression of genes, which are involved in motility and chemotaxis (e.g., hag, fliT) and in acetoin metabolism (e.g., acoABCL), was determined during the fermentation with the mixed nitrogen source of casamino acids and ammonia, indicating a carbon limitation under these fermentation conditions. Under high cell density and slow growth rate conditions a weak up-regulation of autolysis genes could be observed as well as the induction of a number of genes involved in motility, chemotaxis and general stress response. Results of this study allowed the selection of marker genes, which could be used for the monitoring of B. subtilis fermentation processes. The data suggest for example acoA as a marker gene for glucose limitation or glnA as an indicator for nitrogen limitation.

Bacillus subtilis↗

PubMed2002

Evaluation of thresholds for the detection of binding sites for regulatory proteins in Escherichia coli K12 DNA.

BACKGROUND: Sites in DNA that bind regulatory proteins can be detected computationally in various ways. Pattern discovery methods analyze collections of genes suspected to be co-regulated on the evidence, for example, of clustering of transcriptome data. Pattern searching methods use sequences with known binding sites to find other genes regulated by a given protein. Such computational methods are important strategies in the discovery and elaboration of regulatory networks and can provide the experimental biologist with a precise prediction of a binding site or identify a gene as a member of a set of co-regulated genes (a regulon). As more variations on such methods are published, however, thorough evaluation is necessary, as performance may differ depending on the conditions of use. Detailed evaluation also helps to improve and understand the behavior of the different methods and computational strategies. RESULTS: We used a collection of 86 regulons from Escherichia coli as datasets to evaluate two methods for pattern discovery and pattern searching: dyad analysis/dyad sweeping using the program Dyad-analysis, and multiple alignment using the programs Consensus/Patser. Clearly defined statistical parameters are used to evaluate the two methods in different situations. We placed particular emphasis on minimizing the rate of false positives. CONCLUSIONS: As a general rule, sensors obtained from experimentally reported binding sites in DNA frequently locate true sites as the highest-scoring sequences within a given upstream region, especially using Consensus/Patser. Pattern discovery is still an unsolved problem, although in the cases where Dyad-analysis finds significant dyads (around 50%), these frequently correspond to true binding sites. With more robust methods, regulatory predictions could help identify the function of unknown genes.

Bacterial Proteins↗