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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

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

We develop revised theoretical ideas on the mechanism by which the transcription factor proteins locate their specific binding sites on DNA faster than the three-dimensional (3D) diffusion controlled rate limit. We demonstrate that the…

Biological Physics · Physics 2014-09-22 Rajamanickam Murugan

There is now a certain consensus that Transcription Factors (TFs) reach their target sites, where they regulate gene transcription, via a mechanism dubbed facilitated diffusion (FD). In FD, the TF cycles between events of 3D-diffusion in…

Biomolecules · Quantitative Biology 2015-06-18 Carlo Guardiani , Massimo Cencini , Fabio Cecconi

The diffusion-controlled limit of reaction times for site-specific DNA-binding proteins is derived from first principles. We follow the generally accepted concept that a protein propagates via two competitive modes, a three-dimensional…

Biological Physics · Physics 2009-11-11 Konstantin V. Klenin , Holger Merlitz , Joerg Langowski , Chen-Xu Wu

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

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

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

Transcription factors perform facilitated diffusion (3D diffusion in the cytosol and 1D diffusion on the DNA) when binding to their target sites to regulate gene expression. Here, we investigated the influence of this binding mechanism on…

Molecular Networks · Quantitative Biology 2014-09-04 Armin P. Schoech , Nicolae Radu Zabet

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

It is known since the early days of molecular biology that proteins locate their specific targets on DNA up to two orders of magnitude faster than the Smoluchowski 3D diffusion rate. It was the idea due to Delbruck that they are…

Biomolecules · Quantitative Biology 2015-06-26 Tao Hu , A. Yu. Grosberg , B. I. Shklovskii

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

Site-specific transcription factors (TFs) bind to their target sites on the DNA, where they regulate the rate at which genes are transcribed. Bacterial TFs undergo facilitated diffusion (a combination of 3D diffusion around and 1D random…

Molecular Networks · Quantitative Biology 2014-04-23 Daphne Ezer , Nicolae Radu Zabet , Boris Adryan

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

The most common gene regulation mechanism is when a transcription factor protein binds to a regulatory sequence to increase or decrease RNA transcription. However, transcription factors face two main challenges when searching for these…

Quantitative Methods · Quantitative Biology 2023-11-21 Lucas Hedström , Ludvig Lizana

Recognition and binding of specific sites on DNA by proteins is central for many cellular functions such as transcription, replication, and recombination. In the process of recognition, a protein rapidly searches for its specific site on a…

Biomolecules · Quantitative Biology 2007-05-23 Michael Slutsky , Leonid A. Mirny

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

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

Living cells must control the reading out or "expression" of information encoded in their genomes, and this regulation often is mediated by transcription factors--proteins that bind to DNA and either enhance or repress the expression of…

Molecular Networks · Quantitative Biology 2013-08-01 Gašper Tkačik , Aleksandra M Walczak , William Bialek

Transcription factors are able to associate to their binding sites on DNA faster than the physical limit posed by diffusion. Such high association rates can be achieved by alternating between three-dimensional diffusion and one-dimensional…

Biomolecules · Quantitative Biology 2017-12-07 Massimo Cencini , Simone Pigolotti
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