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We study by simulation the effect of the diffusive motion of repressor molecules on the noise in mRNA and protein levels in the case of a repressed gene. We find that spatial fluctuations due to diffusion can drastically enhance the noise…

Molecular Networks · Quantitative Biology 2007-05-23 Jeroen S. van Zon , Marco J. Morelli , Sorin Tanase-Nicola , Pieter Rein ten Wolde

We present a theoretical model of facilitated diffusion of proteins in the cell nucleus. This model, which takes into account the successive binding/unbinding events of proteins to DNA, relies on a fractal description of the chromatin which…

Statistical Mechanics · Physics 2015-05-19 O. Benichou , C. Chevalier , B. Meyer , R. Voituriez

Transcription Factors (TFs) are proteins that regulate gene expression. The regulation mechanism is via the binding of a TF to a specific part of the gene associated with it, the TF's target. The target of a specific TF corresponds to a…

Statistical Mechanics · Physics 2022-09-02 Ori Hachmo , Ariel Amir

It has long been asserted that proteins like transcription factors may locate their target in DNA sequences at rates that surpass by several orders of magnitude the three-dimensional diffusion limit thank to facilitated diffusion, that is…

Biological Physics · Physics 2010-09-27 Ana-Maria Florescu , Marc Joyeux

To ensure fast gene activation, Transcription Factors (TF) use a mechanism known as facilitated diffusion to find their DNA promoter site. Here we analyze such a process where a TF alternates between 3D and 1D diffusion. In the latter (TF…

Subcellular Processes · Quantitative Biology 2015-05-27 Juergen Reingruber , David Holcman

The precision of biochemical signaling is limited by randomness in the diffusive arrival of molecules at their targets. For proteins binding to the specific sites on the DNA and regulating transcription, the ability of the proteins to…

Molecular Networks · Quantitative Biology 2013-08-01 Gasper Tkacik , William Bialek

Cellular responses often require the fast activation or repression of specific genes, which depends on Transcription Factors (TFs) that have to quickly find the promoters of these genes within a large genome. Transcription Factors (TFs)…

Subcellular Processes · Quantitative Biology 2015-09-02 Jérôme Cartailler , Jürgen Reingruber

The model of facilitated diffusion describes how DNA-binding proteins, such as transcription factors (TFs), find their chromosomal targets by combining 3D diffusion through the cytoplasm and 1D sliding along nonspecific DNA sequences. The…

Quantitative Methods · Quantitative Biology 2008-09-08 Gene-Wei Li , Otto G. Berg , Johan Elf

In living cells, proteins combine 3D bulk diffusion and 1D sliding along the DNA to reach a target faster. This process is known as facilitated diffusion, and we investigate its dynamics in the physiologically relevant case of confined DNA.…

Soft Condensed Matter · Physics 2015-06-12 G. Foffano , D. Marenduzzo , E. Orlandini

The regulation of cellular function is often controlled at the level of gene transcription. Such genetic regulation usually consists of interacting networks, whereby gene products from a single network can act to control their own…

Biological Physics · Physics 2009-11-06 Jeff Hasty , Joel Pradines , Milos Dolnik , J. J. Collins

A crucial step in the regulation of gene expression is binding of transcription factor (TF) proteins to regulatory sites along the DNA. But transcription factors act at nanomolar concentrations, and noise due to random arrival of these…

Molecular Networks · Quantitative Biology 2016-02-10 Thomas R. Sokolowski , Aleksandra M. Walczak , William Bialek , Gašper Tkačik

In bacteria, regulatory proteins search for a specific DNA binding target via "facilitated diffusion": a series of rounds of 3D diffusion in the cytoplasm, and 1D linear diffusion along the DNA contour. Using large scale Brownian dynamics…

Biological Physics · Physics 2013-09-05 C. A. Brackley , M. E. Cates , D. Marenduzzo

We derive exact solutions of simplified models for the temporal evolution of the protein concentration within a cell population arbitrarily far from the stationary state. We show that monitoring the dynamics can assist in modeling and…

Biomolecules · Quantitative Biology 2015-05-13 Sandro Azaele , Jayanth R. Banavar , Amos Maritan

Transcription factor (TF) molecules translocate by facilitated diffusion (a combination of 3D diffusion around and 1D random walk on the DNA). Despite the attention this mechanism received in the last 40 years, only a few studies…

Subcellular Processes · Quantitative Biology 2013-09-20 Nicolae Radu Zabet , Boris Adryan

Many transcription factors bind to DNA with a remarkable lack of specificity, so that regulatory binding sites compete with an enormous number of non-regulatory 'decoy' sites. For an auto-regulated gene, we show decoy sites decrease noise…

Molecular Networks · Quantitative Biology 2015-06-05 Anat Burger , Aleksandra M. Walczak , Peter G. Wolynes

Some proteins can find their targets on DNA faster than by pure diffusion in the three-dimensional cytoplasm, through the process of facilitated diffusion: They can loosely bind to DNA and temporarily slide along it, thus being guided by…

Biomolecules · Quantitative Biology 2024-02-27 Michael A. Lomholt , Ralf Metzler

Under dilute in vitro conditions transcription factors rapidly locate their target sequence on DNA by using the facilitated diffusion mechanism. However, whether this strategy of alternating between three-dimensional bulk diffusion and…

Subcellular Processes · Quantitative Biology 2015-06-12 Max Bauer , Ralf Metzler

The diffusive arrival of transcription factors at the promoter sites on the DNA sets a lower bound on how accurately a cell can regulate its protein levels. Using results from the literature on diffusion-influenced reactions, we derive an…

Molecular Networks · Quantitative Biology 2014-10-24 Joris Paijmans , Pieter Rein ten Wolde

Noise in gene expression, either due to inherent stochasticity or to varying inter- and intracellular environment, can generate significant cell-to-cell variability of protein levels in clonal populations. We present a theoretical…

Other Quantitative Biology · Quantitative Biology 2010-04-08 Julia Rausenberger , Christian Fleck , Jens Timmer , Markus Kollmann

Strong experimental and theoretical evidence shows that transcription factors and other specific DNA-binding proteins find their sites using a two-mode search: alternating between 3D diffusion through the cell and 1D sliding along the DNA.…

Biomolecules · Quantitative Biology 2008-06-11 Zeba Wunderlich , Leonid A. Mirny
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