The role of input noise in transcriptional regulation

In the simplest view of transcriptional regulation, the expression of a gene is turned on or off by changes in the concentration of a transcription factor (TF). We use recent data on noise levels in gene expression to show that it should be possible to transmit much more than just one regulatory bit. Realizing this optimal information capacity would require that the dynamic range of TF concentrations used by the cell, the input/output relation of the regulatory module, and th...

Single-cell studies often show significant phenotypic variability due to the stochastic nature of intra-cellular biochemical reactions. When the numbers of molecules, e.g., transcription factors and regulatory enzymes, are in low abundance, fluctuations in biochemical activities become significant and such "noise" can propagate through regulatory cascades in terms of biochemical reaction networks. Here we develop an intuitive, yet fully quantitative method for analyzing how n...

Biological functions are generated as a result of developmental dynamics that form phenotypes governed by genotypes. The dynamical system for development is shaped through genetic evolution following natural selection based on the fitness of the phenotype. Here we study how this dynamical system is robust to noise during development and to genetic change by mutation. We adopt a simplified transcription regulation network model to govern gene expression, which gives a fitness ...

The transcription factors, such as activators and repressors, can interact with the promoter of gene either in a competitive or non-competitive way. In this paper, we construct a stochastic model with non-competitive transcriptional regulatory architecture and develop an analytical theory that re-establishes the experimental results with an improved data fitting. The analytical expressions in the theory allow us to study the nature of the system corresponding to any of its pa...

We typically think of cells as responding to external signals independently by regulating their gene expression levels, yet they often locally exchange information and coordinate. Can such spatial coupling be of benefit for conveying signals subject to gene regulatory noise? Here we extend our information-theoretic framework for gene regulation to spatially extended systems. As an example, we consider a lattice of nuclei responding to a concentration field of a transcriptiona...

Transcription regulation is largely governed by the profile and the dynamics of transcription factors' binding to DNA. Stochastic effects are intrinsic to this dynamics and the binding to functional sites must be controled with a certain specificity for living organisms to be able to elicit specific cellular responses. Specificity stems here from the interplay between binding affinity and cellular abundancy of transcription factor proteins and the binding of such proteins to ...

A recurring motif in gene regulatory networks is transcription factors (TFs) that regulate each other, and then bind to overlapping sites on DNA, where they interact and synergistically control transcription of a target gene. Here, we suggest that this motif maximizes information flow in a noisy network. Gene expression is an inherently noisy process due to thermal fluctuations and the small number of molecules involved. A consequence of multiple TFs interacting at overlappin...

Gene expression is a random or noisy process. The process consists of several random events among which the reinitiation of transcription by RNAP is an important one. The RNAP molecules can bind the gene only after the promoter gets activated by transcription factors. Several transcription factors bind the promoter to put the gene in the active state. The gene turns into inactive state as the bound transcription factors leave the promoter. During the active period of the gene...

Gene regulatory circuits show significant stochastic fluctuations in their circuit signals due to the low copy number of transcription factors. When a gene circuit component is connected to an existing circuit, the dynamic properties of the existing circuit can be affected by the connected component. In this paper, we investigate modularity in the dynamics of the gene circuit based on stochastic fluctuations in the circuit signals. We show that the noise in the output signal ...

Experiments in recent years have vividly demonstrated that gene expression can be highly stochastic. How protein concentration fluctuations affect the growth rate of a population of cells, is, however, a wide open question. We present a mathematical model that makes it possible to quantify the effect of protein concentration fluctuations on the growth rate of a population of genetically identical cells. The model predicts that the population's growth rate depends on how the g...