ترغب بنشر مسار تعليمي؟ اضغط هنا

A stochastic model of supercoiling-dependent transcription

90   0   0.0 ( 0 )
 نشر من قبل Chris Brackley
 تاريخ النشر 2016
  مجال البحث فيزياء علم الأحياء
والبحث باللغة English




اسأل ChatGPT حول البحث

We propose a stochastic model for gene transcription coupled to DNA supercoiling, where we incorporate the experimental observation that polymerases create supercoiling as they unwind the DNA helix, and that these enzymes bind more favourably to regions where the genome is unwound. Within this model, we show that when the transcriptionally induced flux of supercoiling increases, there is a sharp crossover from a regime where torsional stresses relax quickly and gene transcription is random, to one where gene expression is highly correlated and tightly regulated by supercoiling. In the latter regime, the model displays transcriptional bursts, waves of supercoiling, and up-regulation of divergent or bidirectional genes. It also predicts that topological enzymes which relax twist and writhe should provide a pathway to down-regulate transcription. This article has been published in Physical Review Letters, May 2016.



قيم البحث

اقرأ أيضاً

116 - Ziqing Wang , Ming Li 2011
Membrane tubes are important elements for living cells to organize many functions. Experiments have found that membrane tube can be extracted from giant lipid vesicles by a group of kinesin. How these motors cooperate in extracting the fluid-like mem brane tube is still unclear. In this paper, we propose a new cooperation mechanism called two-track-dumbbell model, in which kinesin is regarded as a dumbbell with an end (tail domain) tightly bound onto the fluid-like membrane and the other end (head domain) stepping on or unbinding from the microtubule. Taking account of the elasticity of kinesin molecule and the exclude volume effect of both the head domain and the tail domain of kinesin, which are not considered in previous models, we simulate the growth process of the membrane tube pulled by kinesin motors. Our results indicate that motors along a single microtubule protofilament can generate enough force to extract membrane tubes from vesicles, and the average number of motors pulling the tube is about 8~9. These results are quite different from previous studies (Ref. cite{camp.08}), and further experimental tests are necessary to elucidate the cooperation mechanism.
We study the effect of transcription on the kinetics of DNA supercoiling in 3D by means of Brownian dynamics simulations of a single nucleotide resolution coarse-grained model for double stranded DNA. By accounting for the action of a transcribing RN A polymerase (RNAP), we characterise the geometry and non equilibrium dynamics of the twin supercoiling domains forming on each side of the RNAP. Textbook pictures depict such domains as symmetric, with plectonemes (writhed DNA) appearing close to the RNAP. On the contrary, we find that the twist generated by transcription results in asymmetric domains, with plectonemes formed far from the RNAP. We show that this translates into an action-at-a-distance on DNA-binding proteins: for instance, positive supercoils downstream of an elongating RNAP destabilise nucleosomes long before the transcriptional machinery reaches the histone octamer. To understand these observations we use our framework to quantitatively analyse the relaxation dynamics of supercoiled DNA. We find a striking separation of timescales between twist diffusion, which is a simple and fast process, and writhe relaxation, which is slow and entails multiple steps.
145 - Dipanwita Ghanti 2018
During the initiation stage of protein synthesis, a ribosomal initiation complex (IC) is assembled on a messenger RNA (mRNA) template. In bacteria, the speed and accuracy of this assembly process are regulated by the complementary activities of three essential initiation factors (IFs). Selection of an authentic N-formylmethionyl-transfer RNA (fMet-tRNAtextsuperscript{fMet}) and the canonical, triplet-nucleotide mRNA start codon are crucial events during assembly of a canonical, ribosomal 70S IC. Mis-initiation due to the aberrant selection of an elongator tRNA or a non-canonical start codon are rare events that result in the assembly of a pseudo 70S IC or a non-canonical 70S IC, respectively. Here, we have developed a theoretical model for the stochastic kinetics of canonical-, pseudo-, and non-canonical 70S IC assembly that includes all of the major steps of the IC assembly process that have been observed and characterized in ensemble kinetic-, single-molecule kinetic-, and structural studies of the fidelity of translation initiation. Specifically, we use the rates of the individual steps in the IC assembly process and the formalism of first-passage times to derive exact analytical expressions for the probability distributions for the assembly of canonical-, pseudo- and non-canonical 70S ICs. In order to illustrate the power of this analytical approach, we compare the theoretically predicted first-passage time distributions with the corresponding computer simulation data. We also compare the mean times required for completion of these assemblies with experimental estimates. In addition to generating new, testable hypotheses, our theoretical model can also be easily extended as new experimental 70S IC assembly data become available, thereby providing a versatile tool for interpreting these data and developing advanced models of the mechanism and regulation of translation initiation.
132 - Ziqing Wang , Ming Li 2009
A transition rate model of cargo transport by $N$ molecular motors is proposed. Under the assumption of steady state, the force-velocity curve of multi-motor system can be derived from the force-velocity curve of single motor. Our work shows, in the case of low load, the velocity of multi-motor system can decrease or increase with increasing motor number, which is dependent on the single motor force-velocity curve. And most commonly, the velocity decreases. This gives a possible explanation to some recent
Current models for the folding of the human genome see a hierarchy stretching down from chromosome territories, through A/B compartments and TADs (topologically-associating domains), to contact domains stabilized by cohesin and CTCF. However, molecul ar mechanisms underlying this folding, and the way folding affects transcriptional activity, remain obscure. Here we review physical principles driving proteins bound to long polymers into clusters surrounded by loops, and present a parsimonious yet comprehensive model for the way the organization determines function. We argue that clusters of active RNA polymerases and their transcription factors are major architectural features; then, contact domains, TADs, and compartments just reflect one or more loops and clusters. We suggest tethering a gene close to a cluster containing appropriate factors -- a transcription factory -- increases the firing frequency, and offer solutions to many current puzzles concerning the actions of enhancers, super-enhancers, boundaries, and eQTLs (expression quantitative trait loci). As a result, the activity of any gene is directly influenced by the activity of other transcription units around it in 3D space, and this is supported by Brownian-dynamics simulations of transcription factors binding to cognate sites on long polymers.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا