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Understanding how transcription factors (TFs) regulate mammalian gene expression in space and time is a central topic in biology. To activate a gene, a TF has first to diffuse in the available space of the nucleus until it reaches a target…

Subcellular Processes · Quantitative Biology 2018-11-19 Maxime Woringer , Xavier Darzacq

We develop a theoretical framework on the mechanism of combinatorial binding of transcription factors (TFs) with their specific binding sites on DNA. We consider three possible mechanisms viz. monomer, hetero-oligomer and coordinated…

Subcellular Processes · Quantitative Biology 2016-10-21 R. Murugan

Transcription factors (TFs), the key players in transcriptional regulation, have attracted great experimental attention, yet the functions of most human TFs remain poorly understood. Recent capabilities in genome-wide protein binding…

Molecular Networks · Quantitative Biology 2016-02-23 Yong Fuga Li , Russ B. Altman

Transcription factors (TFs) are key regulators of gene expression. Based on the classical scenario in which the TF search process switches between one-dimensional motion along the DNA molecule and free Brownian motion in the nucleus, we…

Genomics · Quantitative Biology 2010-10-15 Godefroy Malherbe , David Holcman

Co-localization of networks of genes in the nucleus is thought to play an important role in determining gene expression patterns. Based upon experimental data, we built a dynamical model to test whether pure diffusion could account for the…

Molecular Networks · Quantitative Biology 2012-03-06 Jing Kang , Bing Xu , Ye Yao , Wei Lin , Conor Hennessy , Peter Fraser , Jianfeng Feng

Hill function is one of the widely used gene transcription regulation models. Its attribute of fitting may result in a lack of an underlying physical picture, yet the fitting parameters can provide information about biochemical reactions,…

Molecular Networks · Quantitative Biology 2024-03-05 Wenjia Shi , Yao Ma , Peilin Hu , Mi Pang , Xiaona Huang , Yiting Dang , Yuxin Xie , Danni Wu

The connection between chromatin nuclear organization and gene activity is vividly illustrated by the observation that transcriptional coregulation of certain genes appears to be directly influenced by their spatial proximity. This fact…

Genomics · Quantitative Biology 2015-06-15 Marco Di Stefano , Angelo Rosa , Vincenzo Belcastro , Diego di Bernardo , Cristian Micheletti

Biophysicists are modeling conformations of interphase chromosomes, often basing the strengths of interactions between segments distant on the genetic map on contact frequencies determined experimentally. Here, instead, we develop a…

Biomolecules · Quantitative Biology 2015-11-06 C. A. Brackley , J. Johnson , S. Kelly , P. R. Cook , D. Marenduzzo

In eukaryotic genomes, nucleosomes function to compact DNA and to regulate access to it both by simple physical occlusion and by providing the substrate for numerous covalent epigenetic tags. While nucleosome positions in vitro are…

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

Identity, response to external stimuli, and spatial architecture of a living system are central topics of molecular biology. Presently, they are largely seen as a result of the interplay between a gene repertoire and the regulatory…

Molecular Networks · Quantitative Biology 2007-05-23 M. Cosentino Lagomarsino , P. Jona , B. Bassetti

Heterochromatin protein 1 (HP1) participates in establishing and maintaining heterochromatin via its histone modification dependent chromatin interactions. In recent papers HP1 binding to nucleosomal arrays was measured in vitro and…

Biomolecules · Quantitative Biology 2015-06-22 Vladimir B. Teif , Nick Kepper , Klaus Yserentant , Gero Wedemann , Karsten Rippe

Transcription Factors (TFs) are proteins crucial for regulating gene expression. Effective regulation requires the TFs to rapidly bind to their correct target, enabling the cell to respond efficiently to stimuli such as nutrient…

Biological Physics · Physics 2025-12-04 Wencheng Ji , Ori Hachmo , Naama Barkai , Ariel Amir

We propose a protein model based on a hierarchy of constraints that force the protein to follow certain pathways when changing conformation. The model exhibits a first order phase transition, cooperativity and is exactly solvable. It also…

Condensed Matter · Physics 2015-06-25 Alex Hansen , Mogens H. Jensen , Kim Sneppen , Giovanni Zocchi

To regulate a particular gene, a transcription factor (TF) needs to bind a specific genome location. How is this genome address specified amid the presence of ~10^6-10^9 decoy sites? Our analysis of 319 known TF binding motifs clearly…

Genomics · Quantitative Biology 2009-01-21 Leonid A. Mirny , Zeba Wunderlich

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

We report a new mechanism for allelic dominance in regulatory genetic interactions that we call binding dominance. We investigated a biophysical model of gene regulation, where the fractional occupancy of a transcription factor (TF) on the…

Molecular Networks · Quantitative Biology 2016-08-30 Adam H. Porter , Norman A. Johnson , Alexander Y. Tulchinsky

Transcription factors (TFs) interact with a multitude of binding sites on DNA and partner proteins inside cells. We investigate how nonspecific binding/unbinding to such decoy binding sites affects the magnitude and time-scale of random…

Subcellular Processes · Quantitative Biology 2015-04-15 Mohammad Soltani , Pavol Bokes , Zachary Fox , Abhyudai Singh

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

The binding of a transcription factor (TF) to a DNA operator site can initiate or repress the expression of a gene. Computational prediction of sites recognized by a TF has traditionally relied upon knowledge of several cognate sites,…

Biomolecules · Quantitative Biology 2008-11-10 Sahand Jamal Rahi , Peter Virnau , Leonid A. Mirny , Mehran Kardar