The
            <i>lac</i>
            Repressor Displays Facilitated Diffusion in Living Cells

Hammar, Petter; Leroy, Prune; Mahmutovic, Anel; Marklund, Erik; Berg, Otto G.; Elf, Johan

doi:10.1126/science.1221648

Cited by 380 publications

(565 citation statements)

References 54 publications

(33 reference statements)

Supporting

Mentioning

532

Contrasting

Unclassified

Order By: Relevance

“…This conclusion is derived under the assumption that the fraction of regulatory sites on DNA that Bcd binds to is negligible compared to those that are included in the SDID model which should then correspond to other (non-specific) binding sites. In view of the hopping and sliding model of transcription [von Hippel and Berg, 1989] and the typical fraction of time that transcription factors spend bound to non-specific sites [Elf et al, 2007, Hammar et al, 2012 it is very likely that this assumption be valid in the case of Bcd. Given that most intracellular messengers are likely to be subject to binding/unbinding processes, it is likely that similar problems to those discussed here will be found in other systems as well.…”

Section: Discussionmentioning

confidence: 99%

“…This occurs, in particular, if the concentration of non-specific sites is much larger than that of sites that are specific for transcription. In view of the hopping and sliding model of transcription [von Hippel and Berg, 1989, Elf et al, 2007, Hammar et al, 2012, this is , that correspond to the stationary solution of the SDID model with partial degradation and the parameters of table 1. We note that the relationship between [Hb] and [Bcd T ] in this case is more similar to the one observed in [Gregor et al, 2007b] than the one displayed in figure 6 (a).…”

Section: Timescale: Effective Vs Free Diffusion Coefficientsmentioning

confidence: 99%

See 1 more Smart Citation

The effect of reactions on the formation and readout of the gradient of Bicoid

Ipiña

Dawson

2017

Phys. Biol.

View full text Add to dashboard Cite

Abstract. During early development, the establishment of gradients of transcriptional factors determines the patterning of cell fates. The case of Bicoid (Bcd) in Drosophila melanogaster embryos is well documented and studied. There are still controversies as to whether SDD models in which Bcd is Synthesized at one end, then Diffuses and is Degraded can explain the gradient formation within the timescale observed experimentally. The Bcd gradient is observed in embryos that express a Bicoid-eGFP fusion protein (Bcd-GFP) which cannot differentiate if Bcd is freely diffusing or bound to immobile sites. In this work we analyze an SDID model that includes the Interaction of Bcd with binding sites. Using previously determined biophysical parameters we find that this model can explain the gradient formation within the experimentally observed time. Analyzing the differences between the free and bound Bcd distributions we observe that the latter spans over a longer lengthscale. We conclude that deriving the lengthscale from the distribution of Bcd-GFP can lead to an overestimation of the gradient lengthscale and of the degree of cooperativity that explains the distribution of the protein Hunchback whose production is regulated by Bcd.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Timescale: Effective Vs Free Diffusion Coefficientsmentioning

confidence: 99%

The effect of reactions on the formation and readout of the gradient of Bicoid

Ipiña

Dawson

2017

Phys. Biol.

View full text Add to dashboard Cite

show abstract

“…Indeed, in real systems there are many sequences that have structures and chemical compositions similar to the specific sites. 20,33 The protein molecule can be trapped in these semispecific sites for large periods of time, and it is not clear then how the fast search can be accomplished. However, the majority of theoretical models for the facilitated diffusion ignore this effect, assuming that the nonspecifically bound proteins slide along the homogeneous DNA chain with the same diffusion constant.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of the Protein Search for Targets on DNA in the Presence of Traps

2015

View full text Add to dashboard Cite

Protein search for specific binding sites on DNA is a fundamental biological phenomenon associated with the beginning of most major biological processes. It is frequently found that proteins find and recognize their specific targets quickly and efficiently despite the complex nature of protein-DNA interactions in living cells. Although significant experimental and theoretical efforts was made in recent years, the mechanisms of these processes remain not well clarified. We present a theoretical study of the protein target search dynamics in the presence of semi-specific binding sites which are viewed as traps. Our theoretical approach employs a discrete-state stochastic method that accounts for the most important physical and chemical processes in the system. It also leads to a full analytical description for all dynamic properties of the protein search. It is found that the presence of traps can significantly modify the protein search dynamics. This effect depends on the spatial positions of the targets and traps, on distances between them, on the average sliding length of the protein along the DNA, and on the total length of DNA. Theoretical predictions are discussed using simple physical-chemical arguments, and they are also validated with extensive Monte Carlo computer simulations.keywords: protein-DNA interactions, discrete-state stochastic models, first-passage processes 2

show abstract

“…Note however that, although we can in principle estimate the sliding diffusion coefficient D 1 from diffusion properties of the protein in bulk and get an estimate of the typical sliding length (∼ D 1 /k diss ) that is measured in many experiments (in vitro but also in vivo, see e.g. [90]), it is in fact more subtle than expected. Indeed, as it was imagined by Schurr [51], some DNA-binding proteins slide with an helical motion along DNA [34,35].…”

Section: Defining a Physical-meaningful Sliding Timementioning

confidence: 96%

Protein–DNA Electrostatics

Barbi¹,

Paillusson²

2013

Dynamics of Proteins and Nucleic Acids

View full text Add to dashboard Cite

Gene expression and regulation rely on an apparently finely tuned set of reactions between some proteins and DNA. Such DNA-binding proteins have to find specific sequences on very long DNA molecules and they mostly do so in absence of any active process. It has been rapidly recognized that to achieve this task these proteins should be efficient at both searching (i.e. sampling fast relevant parts of DNA) and finding (i.e. recognizing the specific site).A two-mode search and variants of it have been suggested since the 70s to explain either a fast search or an efficient recognition. Combining these two properties at a phenomenological level is however more difficult as they appear to have antagonist roles. To overcome this difficulty, one may simply need to drop the dichotomic view inherent to the two-mode search and look more thoroughly at the set of interactions between DNA-binding proteins and a given 1 arXiv:1311.7496v1 [physics.bio-ph] 29 Nov 2013 DNA segment either specific or non-specific. This chapter demonstrates that, in doing so in a very generic way, one may indeed find a potential reconciliation between a fast search and an efficient recognition. Although a lot remains to be done, this could be the time for a change of paradigm.

show abstract

The lac Repressor Displays Facilitated Diffusion in Living Cells

Cited by 380 publications

References 54 publications

The effect of reactions on the formation and readout of the gradient of Bicoid

The effect of reactions on the formation and readout of the gradient of Bicoid

Dynamics of the Protein Search for Targets on DNA in the Presence of Traps

Protein–DNA Electrostatics

Contact Info

Product

Resources

About