Abstract:
:Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during electron acceptor shifts. Here we propose a qualitative model that accounts for the full breadth of regulated genes by detailing how two global transcription factors (TFs), ArcA and Fnr of E. coli, sense key metabolic redox ratios and act on a genome-wide basis to regulate anabolic, catabolic, and energy generation pathways. We first fill gaps in our knowledge of this transcriptional regulatory network by carrying out ChIP-chip and gene expression experiments to identify 463 regulatory events. We then interfaced this reconstructed regulatory network with a highly curated genome-scale metabolic model to show that ArcA and Fnr regulate >80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Based on the data, we propose a feedforward with feedback trim regulatory scheme, given the extensive repression of catabolic genes by ArcA and extensive activation of chemiosmotic genes by Fnr. We further corroborated this regulatory scheme by showing a 0.71 r(2) (p<1e-6) correlation between changes in metabolic flux and changes in regulatory activity across fermentative and nitrate respiratory conditions. Finally, we are able to relate the proposed model to a wealth of previously generated data by contextualizing the existing transcriptional regulatory network.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Federowicz S,Kim D,Ebrahim A,Lerman J,Nagarajan H,Cho BK,Zengler K,Palsson Bdoi
10.1371/journal.pgen.1004264subject
Has Abstractpub_date
2014-04-03 00:00:00pages
e1004264issue
4eissn
1553-7390issn
1553-7404pii
PGENETICS-D-13-02925journal_volume
10pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Organisms perceive changes in their dietary environment and enact a suite of behavioral and metabolic adaptations that can impact motivational behavior, disease resistance, and longevity. However, the precise nature and mechanism of these dietary responses is not known. We have uncovered a novel link between dietary f...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002668
更新日期:2012-01-01 00:00:00
abstract::Neuronal cargos are differentially targeted to either axons or dendrites, and this polarized cargo targeting critically depends on the interaction between microtubules and molecular motors. From a forward mutagenesis screen, we identified a gain-of-function mutation in the C. elegans α-tubulin gene mec-12 that trigger...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004715
更新日期:2014-11-13 00:00:00
abstract::Dermal hyperpigmentation or Fibromelanosis (FM) is one of the few examples of skin pigmentation phenotypes in the chicken, where most other pigmentation variants influence feather color and patterning. The Silkie chicken is the most widespread and well-studied breed displaying this phenotype. The presence of the domin...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002412
更新日期:2011-12-01 00:00:00
abstract::Ribosome assembly cofactors are widely conserved across all domains of life. One such group, the ribosome-associated GTPases (RA-GTPase), act as molecular switches to coordinate ribosome assembly. We previously identified the Staphylococcus aureus RA-GTPase Era as a target for the stringent response alarmone (p)ppGpp,...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008346
更新日期:2019-08-29 00:00:00
abstract::Bacterial diversification is often observed, but underlying mechanisms are difficult to disentangle and remain generally unknown. Moreover, controlled diversification experiments in ecologically relevant environments are lacking. We studied bacterial diversification in the mammalian gut, one of the most complex bacter...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002107
更新日期:2011-06-01 00:00:00
abstract::The modification of transcriptional regulation has become increasingly appreciated as a major contributor to morphological evolution. However, the role of negative-acting control elements (e.g. silencers) in generating morphological diversity has been generally overlooked relative to positive-acting "enhancer" element...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005279
更新日期:2015-06-26 00:00:00
abstract::Monospermic fertilization is mediated by the extracellular zona pellucida composed of ZP1, ZP2 and ZP3. Sperm bind to the N-terminus of ZP2 which is cleaved after fertilization by ovastacin (encoded by Astl) exocytosed from egg cortical granules to prevent sperm binding. AstlNull mice lack the post-fertilization block...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006580
更新日期:2017-01-23 00:00:00
abstract::Selenium is an important trace element that occurs in proteins in the form of selenocysteine (Sec) and in tRNAs in the form of selenouridine. Recent large-scale metagenomics projects provide an opportunity for understanding global trends in trace element utilization. Herein, we characterized the selenoproteome of the ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000095
更新日期:2008-06-13 00:00:00
abstract::Most of the genetic architecture of schizophrenia (SCZ) has not yet been identified. Here, we apply a novel statistical algorithm called Covariate-Modulated Mixture Modeling (CM3), which incorporates auxiliary information (heterozygosity, total linkage disequilibrium, genomic annotations, pleiotropy) for each single n...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005803
更新日期:2016-01-25 00:00:00
abstract::The Ku complex binds non-specifically to DNA breaks and ensures repair via NHEJ. However, Ku is also known to bind directly to telomeric DNA ends and its presence there is associated with telomere capping, but avoiding NHEJ. How the complex discriminates between a DNA break and a telomeric extremity remains unknown. O...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006479
更新日期:2016-12-08 00:00:00
abstract::Checkpoint pathways regulate genomic integrity in part by blocking anaphase until all chromosomes have been completely replicated, repaired, and correctly aligned on the spindle. In Saccharomyces cerevisiae, DNA damage and mono-oriented or unattached kinetochores trigger checkpoint pathways that bifurcate to regulate ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002176
更新日期:2011-07-01 00:00:00
abstract::Domesticated Asian rice (Oryza sativa) is one of the oldest domesticated crop species in the world, having fed more people than any other plant in human history. We report the patterns of DNA sequence variation in rice and its wild ancestor, O. rufipogon, across 111 randomly chosen gene fragments, and use these to inf...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0030163
更新日期:2007-09-01 00:00:00
abstract::In Drosophila, dosage compensation augments X chromosome-linked transcription in males relative to females. This process is achieved by the Dosage Compensation Complex (DCC), which associates specifically with the male X chromosome. We previously found that the morphology of this chromosome is sensitive to the amounts...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000066
更新日期:2008-05-02 00:00:00
abstract::Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments. This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life. Bacteria have evolved enormous biol...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001296
更新日期:2011-02-10 00:00:00
abstract::Genome-wide association studies (GWAS) have identified >500 common variants associated with quantitative metabolic traits, but in aggregate such variants explain at most 20-30% of the heritable component of population variation in these traits. To further investigate the impact of genotypic variation on metabolic trai...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004147
更新日期:2014-01-30 00:00:00
abstract::Male mammals produce sperm for most of postnatal life and therefore require a robust germ line stem cell system, with precise balance between self-renewal and differentiation. Prior work established doublesex- and mab-3-related transcription factor 1 (Dmrt1) as a conserved transcriptional regulator of male sexual diff...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006293
更新日期:2016-09-01 00:00:00
abstract::The genetics of domestication has been extensively studied ever since the rediscovery of Mendel's law of inheritance and much has been learned about the genetic control of trait differences between crops and their ancestors. Here, we ask how domestication has altered genetic architecture by comparing the genetic archi...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008791
更新日期:2020-05-14 00:00:00
abstract::Seedling establishment is inhibited on media containing high levels (∼ 6%) of glucose or fructose. Genetic loci that overcome the inhibition of seedling growth on high sugar have been identified using natural variation analysis and mutant selection, providing insight into sugar signaling pathways. In this study, a qua...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004213
更新日期:2014-03-13 00:00:00
abstract::Cellular toxicity introduced by protein misfolding threatens cell fitness and viability. Failure to eliminate these polypeptides is associated with various aggregation diseases. In eukaryotes, the ubiquitin proteasome system (UPS) plays a vital role in protein quality control (PQC), by selectively targeting misfolded ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005178
更新日期:2015-04-28 00:00:00
abstract::The evolution of metazoans from their choanoflagellate-like unicellular ancestor coincided with the acquisition of novel biological functions to support a multicellular lifestyle, and eventually, the unique cellular and physiological demands of differentiated cell types such as those forming the nervous, muscle and im...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003804
更新日期:2013-01-01 00:00:00
abstract::Increases in fruit weight of cultivated vegetables and fruits accompanied the domestication of these crops. Here we report on the positional cloning of a quantitative trait locus (QTL) controlling fruit weight in tomato. The derived allele of Cell Size Regulator (CSR-D) increases fruit weight predominantly through enl...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006930
更新日期:2017-08-17 00:00:00
abstract::miRNAs are small RNAs directing many developmental processes by posttranscriptional regulation of protein-coding genes. We uncovered a new role for miR-1-1/133a-2 and miR-1-2/133a-1 clusters in the specification of embryonic cardiomyocytes allowing transition from an immature state characterized by expression of smoot...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003793
更新日期:2013-01-01 00:00:00
abstract::Marine viruses play a critical role not only in the global geochemical cycles but also in the biology and evolution of their hosts. Despite their importance, viral diversity remains underexplored mostly due to sampling and cultivation challenges. Direct sequencing approaches such as viromics has provided new insights ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007018
更新日期:2017-09-25 00:00:00
abstract::The model plant species Arabidopsis thaliana is successful at colonizing land that has recently undergone human-mediated disturbance. To investigate the prehistoric spread of A. thaliana, we applied approximate Bayesian computation and explicit spatial modeling to 76 European accessions sequenced at 876 nuclear loci. ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000075
更新日期:2008-05-16 00:00:00
abstract::The Drosophila genes spalt major (salm) and spalt-related (salr) encode Zn-finger transcription factors regulated by the Decapentaplegic (Dpp) signalling pathway in the wing imaginal disc. The function of these genes is required for cell survival and proliferation in the central region of the wing disc, and also for v...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005370
更新日期:2015-08-04 00:00:00
abstract::Marine ecosystems are changing rapidly as the oceans warm and become more acidic. The physical factors and the changes to ocean chemistry that they drive can all be measured with great precision. Changes in the biological composition of communities in different ocean regions are far more challenging to measure because...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007943
更新日期:2019-02-08 00:00:00
abstract::House dust mites are common pests with an unusual evolutionary history, being descendants of a parasitic ancestor. Transition to parasitism is frequently accompanied by genome rearrangements, possibly to accommodate the genetic change needed to access new ecology. Transposable element (TE) activity is a source of geno...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007183
更新日期:2018-01-29 00:00:00
abstract::Bromodomain proteins are key regulators of gene expression. How the levels of these factors are regulated in specific environmental conditions is unknown. Previous work has established that expression of yeast Bromodomain factor 2 (BDF2) is limited by spliceosome-mediated decay (SMD). Here we show that BDF2 is subject...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004661
更新日期:2014-09-18 00:00:00
abstract::In Saccharomyces cerevisiae, the conserved phosphatase Cdc14 is required for the exit from mitosis. It is anchored on nucleolar chromatin by the Cfi1/Net1 protein until early anaphase, at which time it is released into the nucleoplasm. Two poorly understood, redundant pathways promote Cdc14 release, the FEAR (Cdc four...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000588
更新日期:2009-08-01 00:00:00
abstract::Drosophila bithorax complex (BX-C) is one of the best model systems for studying the role of boundaries (insulators) in gene regulation. Expression of three homeotic genes, Ubx, abd-A, and Abd-B, is orchestrated by nine parasegment-specific regulatory domains. These domains are flanked by boundary elements, which func...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007702
更新日期:2018-12-12 00:00:00