Sat, 19 Jul 2008 00:42:10 BST CiteULike: margaritis's library [192 articles] http://www.citeulike.org/user/margaritis CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/margaritis/article/1902642 <i>J Cell Biol, Vol. 179, No. 2. (22 October 2007), pp. 291-304.</i><br /><br />RNA polymerase II (RNAPII) is a fundamental enzyme, but few studies have analyzed its activity in living cells. Using human immunodeficiency virus (HIV) type 1 reporters, we study real-time messenger RNA (mRNA) biogenesis by photobleaching nascent RNAs and RNAPII at specific transcription sites. Through modeling, the use of mutant polymerases, drugs, and quantitative in situ hybridization, we investigate the kinetics of the HIV-1 transcription cycle. Initiation appears efficient because most polymerases demonstrate stable gene association. We calculate an elongation rate of approximately 1.9 kb/min, and, surprisingly, polymerases remain at transcription sites 2.5 min longer than nascent RNAs. With a total polymerase residency time estimated at 333 s, 114 are assigned to elongation, and 63 are assigned to 3'-end processing and/or transcript release. However, mRNAs were released seconds after polyadenylation onset, and analysis of polymerase density by chromatin immunoprecipitation suggests that they pause or lose processivity after passing the polyA site. The strengths and limitations of this kinetic approach to analyze mRNA biogenesis in living cells are discussed. The transcriptional cycle of HIV-1 in real-time and live cells. S Boireau P Maiuri E Basyuk M de la Mata A Knezevich B Pradet-Balade V Bäcker A Kornblihtt A Marcello E Bertrand doi:10.1083/jcb.200706018 J Cell Biol, Vol. 179, No. 2. (22 October 2007), pp. 291-304. 2007-11-12T12:32:05-00:00 2007 J Cell Biol 0021-9525 179 2 291 304 elongation experiment pauses transcription http://www.citeulike.org/user/margaritis/article/2958782 <i>Mol. Cell. Biol., Vol. 25, No. 9. (1 May 2005), pp. 3543-3552.</i><br /><br />We analyzed the impact of a GAGA element on a transgenic promoter in Drosophila melanogaster that was activated by proteins composed of the Teton DNA binding domain and either the heat shock factor (HSF) activation domain or a potent subdomain of VP16. Permanganate footprinting was used to monitor polymerase II (Pol II) on the transgenic promoters in vivo. Activation by Teton-HSF but not by Teton-VP16A2 required the GAGA element; this correlated with the ability of the GAGA element to establish a paused Pol II. Although the GAGA element was not required for activation by Teton-VP16A2, the GAGA element greatly accelerated the rate of activation. The permanganate data also provided evidence that Pol II encountered different rate-limiting steps, following initiation in the presence of Teton-HSF and Teton-VP16A2. The rate-limiting step in the presence of Teton-HSF was release of Pol II paused about 20 to 40 nucleotides downstream from the start site. The rate-limiting step in the presence of Teton-VP16A2 occurred much closer to the transcription start site. Several biochemical studies have provided evidence for a structural transition shortly after Pol II initiates transcription. The behavior of Pol II in the presence of Teton-VP16A2 provides the first evidence that this transition occurs in vivo. 10.1128/MCB.25.9.3543-3552.2005 Identification In Vivo of Different Rate-Limiting Steps Associated with Transcriptional Activators in the Presence and Absence of a GAGA Element Yunyuan Wang Hongbing Tang David Gilmour doi:10.1128/MCB.25.9.3543-3552.2005 Mol. Cell. Biol., Vol. 25, No. 9. (1 May 2005), pp. 3543-3552. 2008-07-03T11:13:45-00:00 2005 Mol. Cell. Biol. 25 9 3543 3552 initiation pause promoter-proximal transcription http://www.citeulike.org/user/margaritis/article/2926238 <i>Annual Review of Microbiology, Vol. 51, No. 1. (1997), pp. 527-564.</i><br /><br />Abstract In gram-positive bacteria, many important processes are controlled by cell-to-cell communication, which is mediated by extracellular signal molecules produced by the bacteria. Most of these signaling molecules are peptides or modified peptides. Signal processing, in most cases, involves either transduction across the cytoplasmic membrane or import of the signal and subsequent interaction with intracellular effectors. Concentrations of signal in the nanomolar range or below are frequently sufficient for biological activity. The microbial processes controlled by extracellular signaling include the expression of virulence factors, the expression of gene transfer functions, and the production of antibiotics. CELL-CELL COMMUNICATION IN GRAM-POSITIVE BACTERIA Gary Dunny Bettina Leonard doi:10.1146/annurev.micro.51.1.527 Annual Review of Microbiology, Vol. 51, No. 1. (1997), pp. 527-564. 2008-06-25T16:22:58-00:00 1997 Annual Review of Microbiology 51 1 527 564 bacteria cell_singalling http://www.citeulike.org/user/margaritis/article/2926191 <i>Nat Rev Mol Cell Biol, Vol. 3, No. 9. (2002), pp. 685-695.</i> Listening in on bacteria: acyl-homoserine lactone signalling Clay Fuqua Peter Greenberg doi:10.1038/nrm907 Nat Rev Mol Cell Biol, Vol. 3, No. 9. (2002), pp. 685-695. 2008-06-25T15:54:34-00:00 2002 Nat Rev Mol Cell Biol 3 9 685 695 bacteria cell_singalling http://www.citeulike.org/user/margaritis/article/2890237 <i>Science, Vol. 320, No. 5882. (13 June 2008), pp. 1428-1429.</i><br /><br />10.1126/science.1159747 BIOCHEMISTRY: How Enzymes Work Dagmar Ringe Gregory Petsko doi:10.1126/science.1159747 Science, Vol. 320, No. 5882. (13 June 2008), pp. 1428-1429. 2008-06-13T00:22:11-00:00 2008 Science 320 5882 1428 1429 active_site catalysis_mechanism enzymes http://www.citeulike.org/user/margaritis/article/2725259 <i>Biophys. J. (25 April 2008), biophysj.108.131771.</i><br /><br />An alternative theoretical approach to enzyme kinetics that is particularly applicable to single molecule enzymology is presented. The theory, originated by Van Slyke and Cullen in 1914, develops enzyme kinetics from a "time perspective" rather than the traditional "rate perspective", and emphasizes the nonequilibrium steady state nature of enzymatic reactions and the significance of small copy numbers of enzyme molecules in living cells. Sigmoidal cooperative substrate binding to slowly fluctuating, monomeric enzymes is shown to arise from association pathways with very small probability but extremely long passage time, which would be disregarded in the traditional rate perspective: A single enzyme stochastically takes alternative pathways in serial order rather than different pathways in parallel. The theory unifies dynamic cooperativity and Hopfield-Ninio's kinetic proofreading mechanism for specificity amplification. 10.1529/biophysj.108.131771 Cooperativity and Specificity in Enzyme Kinetics: A Single-Molecule Time-based Perspective Hong Qian doi:10.1529/biophysj.108.131771 Biophys. J. (25 April 2008), biophysj.108.131771. 2008-04-28T00:14:32-00:00 2008 Biophys. J. biophysj.108.131771 kinetic_proofreading rate_reactions http://www.citeulike.org/user/margaritis/article/540972 <i>Nature, Vol. 440, No. 7081., pp. 174-180.</i> Stochastic spineless expression creates the retinal mosaic for colour vision Mathias Wernet Esteban Mazzoni Arzu Ãelik Dianne Duncan Ian Duncan Claude Desplan doi:10.1038/nature04615 Nature, Vol. 440, No. 7081., pp. 174-180. 2006-03-08T21:53:15-00:00 Nature 0028-0836 440 7081 174 180 Nature Publishing Group development gene-expression stochasticity vision http://www.citeulike.org/user/margaritis/article/2866443 <i>Molecular Cell, Vol. 30, No. 5. (5 June 2008), pp. 557-566.</i><br /><br />Summary To study fidelity of RNA polymerase II (Pol II), we analyzed properties of the 6-azauracil-sensitive and TFIIS-dependent E1103G mutant of rbp1 (rpo21), the gene encoding the catalytic subunit of Pol II in Saccharomyces cerevisiae. Using an in vivo retrotransposition-based transcription fidelity assay, we observed that rpb1-E1103G causes a 3-fold increase in transcription errors. This mutant showed a 10-fold decrease in fidelity of transcription elongation in vitro. The mutation does not appear to significantly affect translocation state equilibrium of Pol II in a stalled elongation complex. Primarily, it promotes NTP sequestration in the polymerase active center. Furthermore, pre-steady-state analyses revealed that the E1103G mutation shifted the equilibrium between the closed and the open active center conformations toward the closed form. Thus, open conformation of the active center emerges as an intermediate essential for preincorporation fidelity control. Similar mechanisms may control fidelity of DNA-dependent DNA polymerases and RNA-dependent RNA polymerases. Transient Reversal of RNA Polymerase II Active Site Closing Controls Fidelity of Transcription Elongation Maria Kireeva Yuri Nedialkov Gina Cremona Yuri Purtov Lucyna Lubkowska Francisco Malagon Zachary Burton Jeffrey Strathern Mikhail Kashlev doi:10.1016/j.molcel.2008.04.017 Molecular Cell, Vol. 30, No. 5. (5 June 2008), pp. 557-566. 2008-06-05T16:49:27-00:00 2008 Molecular Cell 30 5 557 566 fidelity transcription http://www.citeulike.org/user/margaritis/article/2678830 <i>Nature, Vol. 452, No. 7189. (17 April 2008), pp. 840-845.</i> Evolvability and hierarchy in rewired bacterial gene networks Mark Isalan Caroline Lemerle Konstantinos Michalodimitrakis Carsten Horn Pedro Beltrao Emanuele Raineri Mireia Garriga-Canut Luis Serrano doi:10.1038/nature06847 Nature, Vol. 452, No. 7189. (17 April 2008), pp. 840-845. 2008-04-16T19:45:06-00:00 2008 Nature 452 7189 840 845 Nature Publishing Group evolvability gene-circuits gene-expression gene-networks regulation transcription http://www.citeulike.org/user/margaritis/article/2762804 <i>Mol Syst Biol, Vol. 4 (6 May 2008)</i> Colored extrinsic fluctuations and stochastic gene expression Vahid Shahrezaei Julien Ollivier Peter Swain doi:10.1038/msb.2008.31 Mol Syst Biol, Vol. 4 (6 May 2008) 2008-05-06T20:09:01-00:00 2008 Mol Syst Biol 4 EMBO and Nature Publishing Group extrinsic fluctuations noise stochasticity stochastic_simulations theory http://www.citeulike.org/user/margaritis/article/2678479 <i>Mol Syst Biol, Vol. 4 (15 April 2008)</i> Transient heterogeneity in extracellular protease production by Bacillus subtilis Jan-Willem Veening Oleg Igoshin Robyn Eijlander Reindert Nijland Leendert Hamoen Oscar Kuipers doi:10.1038/msb.2008.18 Mol Syst Biol, Vol. 4 (15 April 2008) 2008-04-16T16:31:01-00:00 2008 Mol Syst Biol 4 EMBO and Nature Publishing Group bistability bsubtilis experiment multistability http://www.citeulike.org/user/margaritis/article/2739852 <i>Nature, Vol. 453, No. 7191., pp. 98-101.</i> Hierarchical structure and the prediction of missing links in networks Aaron Clauset Cristopher Moore MEJ Newman doi:10.1038/nature06830 Nature, Vol. 453, No. 7191., pp. 98-101. 2008-04-30T19:31:59-00:00 Nature 0028-0836 453 7191 98 101 Nature Publishing Group complexity hierarchical networks http://www.citeulike.org/user/margaritis/article/2689148 <i>Proceedings of the National Academy of Sciences (17 April 2008), 0708708105.</i><br /><br />We develop a probabilistic method for analyzing global features of a cellular network under intrinsic statistical fluctuations, which is important when there are finite numbers of molecules. By making a self-consistent mean field approximation of splitting the variables in order to reduce the large number of degrees of freedom, which is reasonable for a not very strongly interacting network, we discovered that the underlying energy landscape of the mitogen-activated protein kinases (MAPKs) signal transduction network (with experimentally measured or inferred parameters such as chemical reaction rate coefficients in the network) is funneled toward a global minimum characterized by the nonequilibrium steady-state fixed point of the system at the end of the signal transduction process. For this system, we also show that the energy landscape is robust against intrinsic fluctuations and random perturbation to the inherent chemical reaction rates. The ratio of the slope versus the roughness of the energy landscape becomes a quantitative measure of robustness and stability of the network. Furthermore, we quantify the dissipation cost of this nonequilibrium system through entropy production, caused by the nonequilibrium flux in the system. We found that a lower dissipation cost corresponds to a more robust network. This least dissipation property might provide a design principle for robust and functional networks. Finally, we find the possibility of bistable and oscillatory-like solutions, which are important for cell fate decisions, upon perturbations. The method described here can be used in a variety of biological networks. 10.1073/pnas.0708708105 Intrinsic noise, dissipation cost, and robustness of cellular networks: The underlying energy landscape of MAPK signal transduction Saul Lapidus Bo Han Jin Wang doi:10.1073/pnas.0708708105 Proceedings of the National Academy of Sciences (17 April 2008), 0708708105. 2008-04-18T18:35:19-00:00 2008 Proceedings of the National Academy of Sciences 0708708105 noise potential regulatory_network stochasticity http://www.citeulike.org/user/margaritis/article/2678240 <i>Proceedings of the National Academy of Sciences, Vol. 105, No. 15. (15 April 2008), pp. 5670-5674.</i><br /><br />Based on a recent ternary complex crystal structure of human DNA polymerase with a G:A mismatch in the active site, we carried out a theoretical investigation of the catalytic mechanism of incorrect nucleotide incorporation using molecular dynamics simulation, quantum mechanics, combined quantum mechanics, and molecular mechanics methods. A two-stage mechanism is proposed with a nonreactive active-site structural rearrangement prechemistry step occurring before the nucleotidyl transfer reaction. The free energy required for formation of the prechemistry state is found to be the major factor contributing to the decrease in the rate of incorrect nucleotide incorporation compared with correct insertion and therefore to fidelity enhancement. Hence, the transition state and reaction barrier for phosphodiester bond formation after the prechemistry state are similar to that for correct insertion reaction. Key residues that provide electrostatic stabilization of the transition state are identified. 10.1073/pnas.0801257105 Incorrect nucleotide insertion at the active site of a G:A mismatch catalyzed by DNA polymerase beta Ping Lin Vinod Batra Lars Pedersen William Beard Samuel Wilson Lee Pedersen doi:10.1073/pnas.0801257105 Proceedings of the National Academy of Sciences, Vol. 105, No. 15. (15 April 2008), pp. 5670-5674. 2008-04-16T14:48:37-00:00 2008 Proceedings of the National Academy of Sciences 105 15 5670 5674 dnap error_rate fidelity http://www.citeulike.org/user/margaritis/article/2678194 <i>Molecular Cell, Vol. 30, No. 1. (11 April 2008), pp. 7-10.</i><br /><br />Recent global analyses have determined that many Drosophila and human genes have engaged polymerase molecules trapped immediately downstream of promoters. These results strongly implicate RNA polymerase II elongation control as a major regulator of differentiation and development. Poised Polymerases: On Your Mark...Get Set...Go! David Price doi:10.1016/j.molcel.2008.03.001 Molecular Cell, Vol. 30, No. 1. (11 April 2008), pp. 7-10. 2008-04-16T14:33:06-00:00 2008 Molecular Cell 30 1 7 10 elongation regulation review transcription http://www.citeulike.org/user/margaritis/article/2669996 <i>Annual Review of Biochemistry, Vol. 69, No. 1. (2000), pp. 497-529.</i><br /><br />Abstract DNA replication fidelity is a key determinant of genome stability and is central to the evolution of species and to the origins of human diseases. Here we review our current understanding of replication fidelity, with emphasis on structural and biochemical studies of DNA polymerases that provide new insights into the importance of hydrogen bonding, base pair geometry, and substrate-induced conformational changes to fidelity. These studies also reveal polymerase interactions with the DNA minor groove at and upstream of the active site that influence nucleotide selectivity, the efficiency of exonucleolytic proofreading, and the rate of forming errors via strand misalignments. We highlight common features that are relevant to the fidelity of any DNA synthesis reaction, and consider why fidelity varies depending on the enzymes, the error, and the local sequence environment. DNA REPLICATION FIDELITY Thomas Kunkel Katarzyna Bebenek doi:10.1146/annurev.biochem.69.1.497 Annual Review of Biochemistry, Vol. 69, No. 1. (2000), pp. 497-529. 2008-04-14T17:37:35-00:00 2000 Annual Review of Biochemistry 69 1 497 529 fidelity proofreading replication http://www.citeulike.org/user/margaritis/article/2667585 <i>Cell, Vol. 132, No. 6. (21 March 2008), pp. 971-982.</i><br /><br />Transcription termination by bacterial RNA polymerase (RNAP) occurs at sequences coding for a GC-rich RNA hairpin followed by a U-rich tract. We used single-molecule techniques to investigate the mechanism by which three representative terminators (his, t500, and tR2) destabilize the elongation complex (EC). For his and tR2 terminators, loads exerted to bias translocation did not affect termination efficiency (TE). However, the force-dependent kinetics of release and the force-dependent TE of a mutant imply a forward translocation mechanism for the t500 terminator. Tension on isolated U-tracts induced transcript release in a manner consistent with RNA:DNA hybrid shearing. We deduce that different mechanisms, involving hypertranslocation or shearing, operate at terminators with different U-tracts. Tension applied to RNA at terminators suggests that closure of the final 2-3 hairpin bases destabilizes the hybrid and that competing RNA structures modulate TE. We propose a quantitative, energetic model that predicts the behavior for these terminators and mutant variants. Applied force reveals mechanistic and energetic details of transcription termination. MH Larson WJ Greenleaf R Landick SM Block doi:10.1016/j.cell.2008.01.027 Cell, Vol. 132, No. 6. (21 March 2008), pp. 971-982. 2008-04-14T12:47:15-00:00 2008 Cell 1097-4172 132 6 971 982 single-molecule termination transcription http://www.citeulike.org/user/margaritis/article/2567082 <i>Proceedings of the National Academy of Sciences (19 March 2008), 0707904105.</i><br /><br />Cis-regulatory control of transcription is the dominant form of regulation of gene expression. Recent experimental results suggest that, in addition to the mean expression level, cell-to-cell variability might also be transcriptionally regulated. Here, we develop a stochastic model of transcriptional regulation that allows us to calculate closed-form analytical expressions for the mean and variance of the protein and mRNA distributions for an arbitrarily complex cis-regulatory motif. Our model allows us to investigate how noise may be transcriptionally regulated independently from the mean expression. We show that our approach is in excellent agreement with stochastic simulations and experiment, and leads to an experimentally testable formula for the noise in gene expression as a function of inducer-molecule concentrations. 10.1073/pnas.0707904105 Transcriptional control of noise in gene expression Alvaro Sanchez Jane Kondev doi:10.1073/pnas.0707904105 Proceedings of the National Academy of Sciences (19 March 2008), 0707904105. 2008-03-20T15:15:36-00:00 2008 Proceedings of the National Academy of Sciences 0707904105 noise regulation stochasticity theory transcription http://www.citeulike.org/user/margaritis/article/2628123 <i>Science, Vol. 320, No. 5872. (4 April 2008), pp. 65-68.</i><br /><br />Fundamental to living cells is the capacity to differentiate into subtypes with specialized attributes. Understanding the way cells acquire their fates is a major challenge in developmental biology. How cells adopt a particular fate is usually thought of as being deterministic, and in the large majority of cases it is. That is, cells acquire their fate by virtue of their lineage or their proximity to an inductive signal from another cell. In some cases, however, and in organisms ranging from bacteria to humans, cells choose one or another pathway of differentiation stochastically, without apparent regard to environment or history. Stochasticity has important mechanistic requirements. We speculate on why stochasticity is advantageousand even critical in some circumstancesto the individual, the colony, or the species. 10.1126/science.1147888 Stochasticity and Cell Fate Richard Losick Claude Desplan doi:10.1126/science.1147888 Science, Vol. 320, No. 5872. (4 April 2008), pp. 65-68. 2008-04-03T23:36:32-00:00 2008 Science 320 5872 65 68 bistability cell_fate review stochasticity http://www.citeulike.org/user/margaritis/article/2606114 <i>Science, Vol. 319, No. 5871. (28 March 2008), pp. 1791-1792.</i><br /><br />Recent work has shown that the RNA polymerase II enzyme pauses at a promoter-proximal site of many genes in Drosophila and mammals. This rate-limiting step occurs after recruitment and initiation of RNA polymerase II at a gene promoter. This stage in early elongation appears to be an important and broadly used target of gene regulation. 10.1126/science.1150843 Transcription Regulation Through Promoter-Proximal Pausing of RNA Polymerase II Leighton Core John Lis doi:10.1126/science.1150843 Science, Vol. 319, No. 5871. (28 March 2008), pp. 1791-1792. 2008-03-28T12:35:34-00:00 2008 Science 319 5871 1791 1792 pause pauses regulation transcription http://www.citeulike.org/user/margaritis/article/2255308 <i>Proceedings of the National Academy of Sciences, Vol. 104, No. 48. (27 November 2007), pp. 18958-18963.</i><br /><br />Detection of different extracellular stimuli leading to functionally distinct outcomes is ubiquitous in cell biology, and is often mediated by differential regulation of positive and negative feedback loops that are a part of the signaling network. In some instances, these cellular responses are stimulated by small numbers of molecules, and so stochastic effects could be important. Therefore, we studied the influence of stochastic fluctuations on a simple signaling model with dueling positive and negative feedback loops. The class of models we have studied is characterized by single deterministic steady states for all parameter values, but the stochastic response is bimodal; a behavior that is distinctly different from models studied in the context of gene regulation. For example, when positive and negative regulation is roughly balanced, a unique deterministic steady state with an intermediate value for the amount of a downstream signaling product is found. However, for small numbers of signaling molecules, stochastic effects result in a bimodal distribution for this quantity, with neither mode corresponding to the deterministic solution; i.e., cells are in "on" or "off" states, not in some intermediate state. For a large number of molecules, the stochastic solution converges to the mean-field result. When fluctuations are important, we find that signal output scales with control parameters "anomalously" compared with mean-field predictions. The necessary and sufficient conditions for the phenomenon we report are quite common. So, our findings are expected to be of broad relevance, and suggest that stochastic effects can enable binary cellular decisions. 10.1073/pnas.0706110104 Purely stochastic binary decisions in cell signaling models without underlying deterministic bistabilities Maxim Artyomov Jayajit Das Mehran Kardar Arup Chakraborty doi:10.1073/pnas.0706110104 Proceedings of the National Academy of Sciences, Vol. 104, No. 48. (27 November 2007), pp. 18958-18963. 2008-01-19T04:51:28-00:00 2007 Proceedings of the National Academy of Sciences 104 48 18958 18963 bistability desicion_making noise http://www.citeulike.org/user/margaritis/article/2601465 <i>Nat Genet, Vol. 40, No. 4. (April 2008), pp. 471-475.</i> Stochastic switching as a survival strategy in fluctuating environments Murat Acar Jerome Mettetal Alexander van Oudenaarden doi:10.1038/ng.110 Nat Genet, Vol. 40, No. 4. (April 2008), pp. 471-475. 2008-03-27T10:36:39-00:00 2008 Nat Genet 40 4 471 475 Nature Publishing Group bistability noise stochasticity http://www.citeulike.org/user/margaritis/article/2601980 <i>Nat Genet, Vol. 40, No. 4. (April 2008), pp. 466-470.</i> Transient-mediated fate determination in a transcriptional circuit of HIV Leor Weinberger Roy Dar Michael Simpson doi:10.1038/ng.116 Nat Genet, Vol. 40, No. 4. (April 2008), pp. 466-470. 2008-03-27T14:04:29-00:00 2008 Nat Genet 40 4 466 470 Nature Publishing Group bistability hiv noise http://www.citeulike.org/user/margaritis/article/154057 <i>Molecular Microbiology, Vol. 56, No. 3. (May 2005), pp. 604-614.</i><br /><br />In Bacillus subtilis competence for genetic transformation develops only in a subpopulation of cells in an isogenic culture. The molecular mechanisms underlying this phenotypic heterogeneity are unknown. In this study, we stepwise simplify the signal transduction cascade leading to competence, yielding a strain devoid of all regulatory inputs for this process that have been identified so far. We demonstrate that auto-stimulation of ComK, the master regulator for competence development, is essential and in itself can be sufficient to generate a bistable expression pattern. We argue that transcriptional regulation determines the threshold of ComK to initiate the auto-stimulatory response, and that the basal level of ComK (in a wild-type strain governed by MecA-mediated proteolytic control) determines the fraction of cells that reach this threshold, and thus develop competence. Stripping Bacillus: ComK auto-stimulation is responsible for the bistable response in competence development Wiep Smits Caroline Eschevins Kim Susanna Sierd Bron Oscar Kuipers Leendert Hamoen doi:10.1111/j.1365-2958.2005.04488.x Molecular Microbiology, Vol. 56, No. 3. (May 2005), pp. 604-614. 2005-04-07T15:09:21-00:00 2005 Molecular Microbiology 0950-382X 56 3 604 614 Blackwell Publishing autoregulation bistability bsubtilis competence http://www.citeulike.org/user/margaritis/article/554114 <i>Nature Reviews Microbiology, Vol. 4, No. 4., pp. 259-271.</i><br /><br />To survive in rapidly changing environmental conditions, bacteria have evolved a diverse set of regulatory pathways that govern various adaptive responses. Recent research has reinforced the notion that bacteria use feedback-based circuitry to generate population heterogeneity in natural situations. Using artificial gene networks, it has been shown that a relatively simple 'wiring' of a bacterial genetic system can generate two or more stable subpopulations within an overall genetically homogeneous population. This review discusses the ubiquity of these processes throughout nature, as well as the presumed molecular mechanisms responsible for the heterogeneity observed in a selection of bacterial species. Phenotypic variation in bacteria: the role of feedback regulation Wiep Smits Oscar Kuipers Jan-Willem Veening doi:10.1038/nrmicro1381 Nature Reviews Microbiology, Vol. 4, No. 4., pp. 259-271. 2006-03-16T11:40:46-00:00 Nature Reviews Microbiology 1740-1526 4 4 259 271 Nature Publishing Group bacteria bistability noise http://www.citeulike.org/user/margaritis/article/154056 <i>Molecular Microbiology, Vol. 56, No. 3. (May 2005), pp. 615-624.</i><br /><br />High expression of the transcriptional activator ComK occurs in 10–20% of the cells in stationary phase cultures of Bacillus subtilis strain 168. ComK drives the expression of more than 100 genes constituting the semidormant K-state, distinct from sporulation and vegetative growth. Among the genes so activated are those that permit competence for genetic transformation. We have addressed the origin of bistability in expression of ComK. We show that bistability requires positive autoregulation at the promoter of comK, but not a potential toggle switch, in which ComK represses the promoter of rok and Rok represses the promoter of comK. We further address the source of the noise that results in the stochastic selection of cells that will express comK. A revised model for the regulation of comK expression is proposed that partially explains bistability. Bistability in the Bacillus subtilis K-state (competence) system requires a positive feedback loop Hedia Maamar David Dubnau doi:10.1111/j.1365-2958.2005.04592.x Molecular Microbiology, Vol. 56, No. 3. (May 2005), pp. 615-624. 2005-04-07T15:09:21-00:00 2005 Molecular Microbiology 0950-382X 56 3 615 624 Blackwell Publishing bistability bsubtilis competence http://www.citeulike.org/user/margaritis/article/2315167 <i>Mol Microbiol, Vol. 67, No. 2. (20 December 2007), pp. 254-263.</i><br /><br />Biofilms of Bacillus subtilis consist of long chains of cells that are held together in bundles by an extracellular matrix of exopolysaccharide and the protein TasA. The exopolysaccharide is produced by enzymes encoded by the epsA-O operon and the gene encoding TasA is located in the yqxM-sipW-tasA operon. Both operons are under the control of the repressor SinR. Derepression is mediated by the antirepressor SinI, which binds to SinR with a 1:1 stoichiometry. Paradoxically, in medium promoting derepression of the matrix operons, the overall concentration of SinR in the culture greatly exceeded that of SinI. We show that under biofilm-promoting conditions sinI, which is under the control of the response regulator Spo0A, was expressed only in a small subpopulation of cells, whereas sinR was expressed in almost all cells. Activation of Spo0A is known to be subject to a bistable switch, and we infer that SinI reaches levels sufficient to trigger matrix production only in the subpopulation of cells in which Spo0A is active. Additionally, evidence suggests that sinI is expressed at intermediate, but not low or high, levels of Spo0A activity, which may explain why certain nutritional conditions are more effective in promoting biofilm formation than others. Bistability and biofilm formation in Bacillus subtilis. Yunrong Chai Frances Chu Roberto Kolter Richard Losick doi:10.1111/j.1365-2958.2007.06040.x Mol Microbiol, Vol. 67, No. 2. (20 December 2007), pp. 254-263. 2008-01-31T14:54:24-00:00 2007 Mol Microbiol 0950-382X 67 2 254 263 biofilm bistability bsubtilis http://www.citeulike.org/user/margaritis/article/204589 <i>Molecular Microbiology, Vol. 56, No. 6. (June 2005), pp. 1481-1494.</i><br /><br />Spore formation in the Gram-positive bacterium Bacillus subtilis is a last resort adaptive response to starvation. To initiate sporulation, the key regulator in this process, Spo0A, needs to be activated by the so-called phosphorelay. Within a sporulating culture of B. subtilis, some cells initiate this developmental program, while other cells do not. Therefore, initiation of sporulation appears to be a regulatory process with a bistable outcome. Using a single cell analytical approach, we show that the autostimulatory loop of spo0A is responsible for generating a bistable response resulting in phenotypic variation within the sporulating culture. It is demonstrated that the main function of RapA, a phosphorelay phosphatase, is to maintain the bistable sporulation gene expression. As rapA expression is quorum regulated, it follows that quorum sensing influences sporulation bistability. Deletion of spo0E, a phosphatase directly acting on Spo0A~P, resulted in abolishment of the bistable expression pattern. Artificial induction of a heterologous Rap phosphatase restored heterogeneity in a rapA or spo0E mutant. These results demonstrate that with external phosphatases, B. subtilis can use the phosphorelay as a tuner to modulate the bistable outcome of the sporulating culture. This shows that B. subtilis employs multiple pathways to maintain the bistable nature of a sporulating culture, stressing the physiological importance of this phenomenon. Phosphatases modulate the bistable sporulation gene expression pattern in Bacillus subtilis Jan-Willem Veening Leendert Hamoen Oscar Kuipers doi:10.1111/j.1365-2958.2005.04659.x Molecular Microbiology, Vol. 56, No. 6. (June 2005), pp. 1481-1494. 2005-05-19T08:03:00-00:00 2005 Molecular Microbiology 0950-382X 56 6 1481 1494 Blackwell Publishing bsubtilis noise sporulation http://www.citeulike.org/user/margaritis/article/746475 <i>Molecular Microbiology, Vol. 61, No. 3. (August 2006), pp. 564-572.</i><br /><br />Gene expression in bacteria is traditionally studied from the average behaviour of cells in a population, which has led to the assumption that under a particular set of conditions all cells express genes in an approximately uniform manner. The advent of methods for visualizing gene expression in individual cells reveals, however, that populations of genetically identical bacteria are sometimes heterogeneous, with certain genes being expressed in a non-uniform manner across the population. In some cases, heterogeneity is manifested by the bifurcation into distinct subpopulations, and we adopt the common usage, referring to this phenomenon as bistability. Here we consider four cases of bistability, three from Bacillus subtilis and one from Escherichia coli, with an emphasis on random switching mechanisms that generate alternative cell states and the biological significance of phenotypic heterogeneity. A review describing additional examples of bistability in bacteria has been published recently. Bistability in bacteria Dubnau David Losick Richard doi:10.1111/j.1365-2958.2006.05249.x Molecular Microbiology, Vol. 61, No. 3. (August 2006), pp. 564-572. 2006-07-08T03:36:48-00:00 2006 Molecular Microbiology 0950-382X 61 3 564 572 Blackwell Publishing bacteria bistability bsubtilis competence http://www.citeulike.org/user/margaritis/article/1167061 <i>Molecular Microbiology, Vol. 63, No. 6. (March 2007), pp. 1806-1816.</i><br /><br />Bacillus subtilis cell population divides into a competent fraction and a non-competent fraction in the stationary phase. The transition from the non-competent state (with basal ComK concentration) to the K-state (with high ComK concentration) behaves like a bistable switch. To better understand the mechanism that sets the fraction of cells that switch into the K-state (K-fraction), we characterized the basal comK expression in individual non-competent cells and found a large cell-to-cell variation. Basal expression rate increased exponentially, reached a maximum and decreased towards zero in the stationary phase. Concomitantly, the intrinsic switching rate increased and decreased with a time lag. When switching was induced prematurely by reduction of ComK proteolysis, the K-fraction increased strongly. Our data support a model in which the average basal level of ComK raises during late exponential phase and due to noise in basal comK expression only those cells that are on the high end of comK expression trigger the autocatalytic feedback for ComK transcription. We show that a subsequent shut-down of basal expression rate sets a ‘time-window’ for switching and is thus involved in determining the K-fraction in the bimodal population. Basal expression rate of comK sets a switching-window into the K-state of Bacillus subtilis Leisner Madeleine Stingl Kerstin Radler O Joachim Maier Berenike doi:10.1111/j.1365-2958.2007.05628.x Molecular Microbiology, Vol. 63, No. 6. (March 2007), pp. 1806-1816. 2007-03-16T05:55:45-00:00 2007 Molecular Microbiology 0950-382X 63 6 1806 1816 Blackwell Publishing bsubtilis competence http://www.citeulike.org/user/margaritis/article/2563904 <i>Cell, Vol. 130, No. 1. (13 July 2007), pp. 77-88.</i><br /><br />We describe the results of a genome-wide analysis of human cells that suggests that most protein-coding genes, including most genes thought to be transcriptionally inactive, experience transcription initiation. We found that nucleosomes with H3K4me3 and H3K9,14Ac modifications, together with RNA polymerase II, occupy the promoters of most protein-coding genes in human embryonic stem cells. Only a subset of these genes produce detectable full-length transcripts and are occupied by nucleosomes with H3K36me3 modifications, a hallmark of elongation. The other genes experience transcription initiation but show no evidence of elongation, suggesting that they are predominantly regulated at postinitiation steps. Genes encoding most developmental regulators fall into this group. Our results also identify a class of genes that are excluded from experiencing transcription initiation, at which mechanisms that prevent initiation must predominate. These observations extend to differentiated cells, suggesting that transcription initiation at most genes is a general phenomenon in human cells. A chromatin landmark and transcription initiation at most promoters in human cells. MG Guenther SS Levine LA Boyer R Jaenisch RA Young doi:10.1016/j.cell.2007.05.042 Cell, Vol. 130, No. 1. (13 July 2007), pp. 77-88. 2008-03-19T18:19:40-00:00 2007 Cell 0092-8674 130 1 77 88 elongation initiation regulation transcription http://www.citeulike.org/user/margaritis/article/1059761 <i>Science, Vol. 315, No. 5810. (19 January 2007), pp. 370-373.</i><br /><br />Cells both actively generate and sensitively react to forces through their mechanical framework, the cytoskeleton, which is a nonequilibrium composite material including polymers and motor proteins. We measured the dynamics and mechanical properties of a simple three-component model system consisting of myosin II, actin filaments, and cross-linkers. In this system, stresses arising from motor activity controlled the cytoskeletal network mechanics, increasing stiffness by a factor of nearly 100 and qualitatively changing the viscoelastic response of the network in an adenosine triphosphate-dependent manner. We present a quantitative theoretical model connecting the large-scale properties of this active gel to molecular force generation. Nonequilibrium mechanics of active cytoskeletal networks. D Mizuno C Tardin CF Schmidt FC Mackintosh doi:10.1126/science.1134404 Science, Vol. 315, No. 5810. (19 January 2007), pp. 370-373. 2007-01-22T13:22:28-00:00 2007 Science 1095-9203 315 5810 370 373 active networks http://www.citeulike.org/user/margaritis/article/2550700 <i>Cell, Vol. 126, No. 2. (28 July 2006), pp. 403-413.</i><br /><br />Summary The expression of a single odorant receptor (OR) gene from a large gene family in individual sensory neurons is an essential feature of the organization and function of the olfactory system. We have used chromosome conformation capture to demonstrate the specific association of an enhancer element, H, on chromosome 14 with multiple OR gene promoters on different chromosomes. DNA and RNA fluorescence in situ hybridization (FISH) experiments allow us to visualize the colocalization of the H enhancer with the single OR allele that is transcribed in a sensory neuron. In transgenic mice bearing additional H elements, sensory neurons that express OR pseudogenes also express a second functional receptor. These data suggest a model of receptor choice in which a single trans-acting enhancer element may allow the stochastic activation of only one OR allele in an olfactory sensory neuron. Interchromosomal Interactions and Olfactory Receptor Choice Stavros Lomvardas Gilad Barnea David Pisapia Monica Mendelsohn Jennifer Kirkland Richard Axel doi:10.1016/j.cell.2006.06.035 Cell, Vol. 126, No. 2. (28 July 2006), pp. 403-413. 2008-03-18T12:02:56-00:00 2006 Cell 126 2 403 413 desicion_making olfactory_genes http://www.citeulike.org/user/margaritis/article/1395953 <i>Nature Reviews Genetics, Vol. 8, No. 7. (05 June 2007), pp. 507-517.</i> The nuclear envelope and transcriptional control Asifa Akhtar Susan Gasser doi:10.1038/nrg2122 Nature Reviews Genetics, Vol. 8, No. 7. (05 June 2007), pp. 507-517. 2007-06-18T06:58:54-00:00 2007 Nature Reviews Genetics 1471-0056 8 7 507 517 Nature Publishing Group control dna regulation transcription http://www.citeulike.org/user/margaritis/article/1048850 <i>Nat Rev Genet, Vol. 8, No. 2. (February 2007), pp. 104-115.</i> Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions Christian Lanctot Thierry Cheutin Marion Cremer Giacomo Cavalli Thomas Cremer doi:10.1038/nrg2041 Nat Rev Genet, Vol. 8, No. 2. (February 2007), pp. 104-115. 2007-01-18T11:53:14-00:00 2007 Nat Rev Genet 8 2 104 115 chromosomes dna organisation http://www.citeulike.org/user/margaritis/article/2010641 <i>Nature Genetics, Vol. 39, No. 12. (11 November 2007), pp. 1507-1511.</i> RNA polymerase is poised for activation across the genome Ginger Muse Daniel Gilchrist Sergei Nechaev Ruchir Shah Joel Parker Sherry Grissom Julia Zeitlinger Karen Adelman doi:10.1038/ng.2007.21 Nature Genetics, Vol. 39, No. 12. (11 November 2007), pp. 1507-1511. 2007-11-29T05:41:46-00:00 2007 Nature Genetics 1061-4036 39 12 1507 1511 Nature Publishing Group elongation pauses regulation rnap transcription http://www.citeulike.org/user/margaritis/article/2010640 <i>Nature Genetics, Vol. 39, No. 12. (11 November 2007), pp. 1512-1516.</i> RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo Julia Zeitlinger Alexander Stark Manolis Kellis Joung-Woo Hong Sergei Nechaev Karen Adelman Michael Levine Richard Young doi:10.1038/ng.2007.26 Nature Genetics, Vol. 39, No. 12. (11 November 2007), pp. 1512-1516. 2007-11-29T05:41:46-00:00 2007 Nature Genetics 1061-4036 39 12 1512 1516 Nature Publishing Group elongation pauses rnap http://www.citeulike.org/user/margaritis/article/2413970 <i>Mol Syst Biol, Vol. 4 (12 February 2008)</i> Modular cell biology: retroactivity and insulation Domitilla Del Vecchio Alexander Ninfa Eduardo Sontag doi:10.1038/msb4100204 Mol Syst Biol, Vol. 4 (12 February 2008) 2008-02-22T11:05:12-00:00 2008 Mol Syst Biol 4 EMBO and Nature Publishing Group control_theory gene-expression gene-networks http://www.citeulike.org/user/margaritis/article/2384447 <i>Proceedings of the National Academy of Sciences, Vol. 105, No. 6. (12 February 2008), pp. 1897-1900.</i><br /><br />Cells are dynamical systems of biomolecular interactions that process information from their environment to mount diverse yet specific responses. A key property of many self-organized systems is that of criticality: a state of a system in which, on average, perturbations are neither dampened nor amplified, but are propagated over long temporal or spatial scales. Criticality enables the coordination of complex macroscopic behaviors that strike an optimal balance between stability and adaptability. It has long been hypothesized that biological systems are critical. Here, we address this hypothesis experimentally for system-wide gene expression dynamics in the macrophage. To this end, we have developed a method, based on algorithmic information theory, to assess macrophage criticality, and we have validated the method on networks with known properties. Using global gene expression data from macrophages stimulated with a variety of Toll-like receptor agonists, we found that macrophage dynamics are indeed critical, providing the most compelling evidence to date for this general principle of dynamics in biological systems. 10.1073/pnas.0711525105 Gene expression dynamics in the macrophage exhibit criticality Matti Nykter Nathan Price Maximino Aldana Stephen Ramsey Stuart Kauffman Leroy Hood Olli Yli-Harja Ilya Shmulevich doi:10.1073/pnas.0711525105 Proceedings of the National Academy of Sciences, Vol. 105, No. 6. (12 February 2008), pp. 1897-1900. 2008-02-15T09:33:45-00:00 2008 Proceedings of the National Academy of Sciences 105 6 1897 1900 adaptability criticality gene-expression robustness http://www.citeulike.org/user/margaritis/article/2288293 <i>Science, Vol. 319, No. 5862. (25 January 2008), pp. 466-469.</i><br /><br />For gene regulation, some transcriptional activators bind periodically to promoters with either a fast ([~]1 minute) or a slow ([~]15 to 90 minutes) cycle. It is uncertain whether the fast cycle occurs on natural promoters, and the function of either cycle in transcription remains unclear. We report that fast and slow cycling can occur simultaneously on an endogenous yeast promoter and that slow cycling in this system reflects an oscillation in the fraction of accessible promoters rather than the recruitment and release of stably bound transcriptional activators. This observation, combined with single-cell measurements of messenger RNA (mRNA) production, argues that fast cycling initiates transcription and that slow cycling regulates the quantity of mRNA produced. These findings counter the prevailing view that slow cycling initiates transcription. 10.1126/science.1150559 Concurrent Fast and Slow Cycling of a Transcriptional Activator at an Endogenous Promoter Tatiana Karpova Min Kim Corentin Spriet Kip Nalley Timothy Stasevich Zoulika Kherrouche Laurent Heliot James Mcnally doi:10.1126/science.1150559 Science, Vol. 319, No. 5862. (25 January 2008), pp. 466-469. 2008-01-25T07:02:07-00:00 2008 Science 319 5862 466 469 binding dna promoter transcription transcription-factor http://www.citeulike.org/user/margaritis/article/2288327 <i>Science, Vol. 319, No. 5862. (25 January 2008), pp. 482-484.</i><br /><br />The propagation of information through signaling cascades spans a wide range of time scales, including the rapid ligand-receptor interaction and the much slower response of downstream gene expression. To determine which dynamic range dominates a response, we used periodic stimuli to measure the frequency dependence of signal transduction in the osmo-adaptation pathway of Saccharomyces cerevisiae. We applied system identification methods to infer a concise predictive model. We found that the dynamics of the osmo-adaptation response are dominated by a fast-acting negative feedback through the kinase Hog1 that does not require protein synthesis. After large osmotic shocks, an additional, much slower, negative feedback through gene expression allows cells to respond faster to future stimuli. 10.1126/science.1151582 The Frequency Dependence of Osmo-Adaptation in Saccharomyces cerevisiae Jerome Mettetal Dale Muzzey Carlos Gomez-Uribe Alexander van Oudenaarden doi:10.1126/science.1151582 Science, Vol. 319, No. 5862. (25 January 2008), pp. 482-484. 2008-01-25T07:19:00-00:00 2008 Science 319 5862 482 484 gene-circuits gene-expression gene-networks gene-regulation negative_feedback http://www.citeulike.org/user/margaritis/article/2291150 <i>J. Bacteriol., Vol. 189, No. 24. (15 December 2007), pp. 8772-8785.</i><br /><br />Transcription elongation factor GreA induces nucleolytic activity of bacterial RNA polymerase (RNAP). In vitro, transcript cleavage by GreA contributes to transcription efficiency by (i) suppressing pauses and arrests, (ii) stimulating RNAP promoter escape, and (iii) enhancing transcription fidelity. However, it is unclear which of these functions is (are) most relevant in vivo. By comparing global gene expression profiles of Escherichia coli strains lacking Gre factors and strains expressing either the wild type (wt) or a functionally inactive GreA mutant, we identified genes that are potential targets of GreA action. Data analysis revealed that in the presence of chromosomally expressed GreA, 19 genes are upregulated; an additional 105 genes are activated upon overexpression of the wt but not the mutant GreA. Primer extension reactions with selected transcription units confirmed the gene array data. The most prominent stimulatory effect (threefold to about sixfold) of GreA was observed for genes of ribosomal protein operons and the tna operon, suggesting that transcript cleavage by GreA contributes to optimal expression levels of these genes in vivo. In vitro transcription assays indicated that the stimulatory effect of GreA upon the transcription of these genes is mostly due to increased RNAP recycling due to facilitated promoter escape. We propose that transcript cleavage during early stages of initiation is thus the main in vivo function of GreA. Surprisingly, the presence of the wt GreA also led to the decreased transcription of many genes. The mechanism of this effect is unknown and may be indirect. 10.1128/JB.00911-07 Analysis of Promoter Targets for Escherichia coli Transcription Elongation Factor GreA In Vivo and In Vitro Ekaterina Stepanova Jookyung Lee Maria Ozerova Ekaterina Semenova Kirill Datsenko Barry Wanner Konstantin Severinov Sergei Borukhov doi:10.1128/JB.00911-07 J. Bacteriol., Vol. 189, No. 24. (15 December 2007), pp. 8772-8785. 2008-01-25T18:38:33-00:00 2007 J. Bacteriol. 189 24 8772 8785 backtracking grea pauses transcription http://www.citeulike.org/user/margaritis/article/2250511 <i>Science, Vol. 319, No. 5861. (18 January 2008), pp. 339-343.</i><br /><br />Many cellular components are present in such low numbers per cell that random births and deaths of individual molecules can cause substantial "noise" in concentrations. But biochemical events do not necessarily occur in single steps of individual molecules. Some processes are greatly randomized when synthesis or degradation occurs in large bursts of many molecules during a short time interval. Conversely, each birth or death of a macromolecule could involve several small steps, creating a memory between individual events. We present a generalized theory for stochastic gene expression, formulating the variance in protein abundance in terms of the randomness of the individual gene expression events. We show that common types of molecular mechanisms can produce gestation and senescence periods that reduce noise without requiring higher abundances, shorter lifetimes, or any concentration-dependent control loops. We also show that most single-cell experimental methods cannot distinguish between qualitatively different stochastic principles, although this in turn makes such methods better suited for identifying which components introduce fluctuations. Characterizing the random events that give rise to noise in concentrations instead requires dynamic measurements with single-molecule resolution. 10.1126/science.1144331 Effects of Molecular Memory and Bursting on Fluctuations in Gene Expression Juan Pedraza Johan Paulsson doi:10.1126/science.1144331 Science, Vol. 319, No. 5861. (18 January 2008), pp. 339-343. 2008-01-18T10:34:03-00:00 2008 Science 319 5861 339 343 bursting fluctuations gene-expression noise stochasticity http://www.citeulike.org/user/margaritis/article/2010561 <i>Nature (28 November 2007)</i> RNA-mediated epigenetic programming of a genome-rearrangement pathway Mariusz Nowacki Vikram Vijayan Yi Zhou Klaas Schotanus Thomas Doak Laura Landweber doi:10.1038/nature06452 Nature (28 November 2007) 2007-11-29T05:38:48-00:00 2007 Nature 0028-0836 Nature Publishing Group dna epigenetics rearrangement rna http://www.citeulike.org/user/margaritis/article/2210656 <i>Biophys. J. (24 August 2007), biophysj.107.105767.</i><br /><br />Transcription is a vital stage in the process of gene expression and a major contributor to fluctuations in gene expression levels for which it is typically modelled as a single step process with Poisson statistics. However, recent single molecule experiments raise questions about the validity of such a simple single step picture. We present a molecular multi-step model of transcription elongation that demonstrates that transcription times are in general non-Poisson distributed. In particular, we model transcriptional pauses due to backtracking of the RNA polymerase as a first passage process. By including such pauses, we obtain a broad, heavy-tailed distribution of transcription elongation times, which can be significantly longer than would be otherwise. When transcriptional pauses result in long transcription times, we demonstrate that this naturally leads to bursts of mRNA production and non-Poisson statistics of mRNA levels. These results suggest that transcriptional pauses may be a significant contributor to the variability in transcription rates with direct implications for noise in cellular processes as well as variability between cells. 10.1529/biophysj.107.105767 Fluctuations, pauses and backtracking in DNA transcription Margaritis Voliotis Netta Cohen Carmen Molina-Paris Tanniemola Liverpool doi:10.1529/biophysj.107.105767 Biophys. J. (24 August 2007), biophysj.107.105767. 2008-01-09T11:21:56-00:00 2007 Biophys. J. biophysj.107.105767 backtracking fluctuations noise stochasticity transcription http://www.citeulike.org/user/margaritis/article/2196366 <i>Proc Natl Acad Sci U S A (28 December 2007)</i><br /><br />Single-pair fluorescence resonance energy transfer was used to track RNA exiting from RNA polymerase II (Pol II) in elongation complexes. Measuring the distance between the RNA 5' end and three known locations within the elongation complex allows us determine its position by means of triangulation. RNA leaves the polymerase active center cleft via the previously proposed exit tunnel and then disengages from the enzyme surface. When the RNA reaches lengths of 26 and 29 nt, its 5' end associates with Pol II at the base of the dock domain. Because the initiation factor TFIIB binds to the dock domain and exit tunnel, exiting RNA may prevent TFIIB reassociation during elongation. RNA further extends toward the linker connecting to the polymerase C-terminal repeat domain (CTD), which binds the 5'-capping enzyme and other RNA processing factors. Single-molecule tracking of mRNA exiting from RNA polymerase II. Joanna Andrecka Robert Lewis Florian Brückner Elisabeth Lehmann Patrick Cramer Jens Michaelis doi:10.1073/pnas.0703815105 Proc Natl Acad Sci U S A (28 December 2007) 2008-01-05T05:32:26-00:00 2007 Proc Natl Acad Sci U S A 1091-6490 mrnap polymerase rnap transcription http://www.citeulike.org/user/margaritis/article/2148169 <i>Nature, Vol. 450, No. 7173. (20 December 2007), pp. 1249-1252.</i> Stochastic gene expression out-of-steady-state in the cyanobacterial circadian clock Jeffrey Chabot Juan Pedraza Prashant Luitel Alexander van Oudenaarden doi:10.1038/nature06395 Nature, Vol. 450, No. 7173. (20 December 2007), pp. 1249-1252. 2007-12-19T19:53:09-00:00 2007 Nature 450 7173 1249 1252 Nature Publishing Group experiment gene-expression noise stochasticity http://www.citeulike.org/user/margaritis/article/2135819 <i>Nat Rev Genet (11 December 2007)</i><br /><br />Genome-scale analyses have allowed us to progress beyond studying gene expression at the level of individual components of a given process by providing global information about functional connections between genes, mRNAs and their regulatory proteins. Such analyses have greatly increased our understanding of the interplay between different events in gene regulation and have highlighted previously unappreciated functional connections, including coupling between nuclear and cytoplasmic processes. Genome-wide approaches have also revealed extensive coordination within regulatory levels, such as the organization of transcription factors into regulatory motifs. Overall, these studies enhance our understanding of how the many components of the eukaryotic cell function as a system to allow both coordination and versatility in gene expression. Coupling and coordination in gene expression processes: a systems biology view. Suzanne Komili Pamela A Silver doi:10.1038/nrg2223 Nat Rev Genet (11 December 2007) 2007-12-17T10:42:16-00:00 2007 Nat Rev Genet 1471-0064 eykaryotic gene-expression review http://www.citeulike.org/user/margaritis/article/2063478 <i>Nat Struct Mol Biol, Vol. 14, No. 12. (December 2007), pp. 1122-1123.</i> Merging the RNA and DNA worlds Irina Artsimovitch Dmitry Vassylyev doi:10.1038/nsmb1207-1122 Nat Struct Mol Biol, Vol. 14, No. 12. (December 2007), pp. 1122-1123. 2007-12-05T18:07:55-00:00 2007 Nat Struct Mol Biol 14 12 1122 1123 Nature Publishing Group pol_ii rnap transcription http://www.citeulike.org/user/margaritis/article/2063427 <i>Nat Struct Mol Biol, Vol. 14, No. 12. (December 2007), pp. 1127-1133.</i> Mechanism of transcriptional stalling at cisplatin-damaged DNA Gerke Damsma Aaron Alt Florian Brueckner Thomas Carell Patrick Cramer doi:10.1038/nsmb1314 Nat Struct Mol Biol, Vol. 14, No. 12. (December 2007), pp. 1127-1133. 2007-12-05T17:49:44-00:00 2007 Nat Struct Mol Biol 14 12 1127 1133 Nature Publishing Group pause rnap stalling transcription