Related papers: Biophysical Fitness Landscapes for Transcription F…
From the response to external stimuli to cell division and death, the dynamics of living cells is based on the expression of specific genes at specific times. The decision when to express a gene is implemented by the binding and unbinding…
Darwinian evolution is driven by random mutations, genetic recombination (gene shuffling) and selection that favors genotypes with high fitness. For systems where each genotype can be represented as a bitstring of length $L$, an overview of…
Transcription factors (TFs) regulate gene expression by binding to specific genomic loci determined by DNA sequence. Their sequence specificity is commonly summarized by a consensus binding motif. However, eukaryotic genomes contain…
DNA shape readout is an important mechanism of target site recognition by transcription factors, in addition to the sequence readout. Several models of transcription factor-DNA binding which consider DNA shape have been developed in recent…
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…
Random walks on multidimensional nonlinear landscapes are of interest in many areas of science and engineering. In particular, properties of adaptive trajectories on fitness landscapes determine population fates and thus play a central role…
Transcription factors (TFs) are proteins that bind to specific sites on the DNA and regulate gene activity. Identifying where TF molecules bind and how much time they spend on their target sites is key for understanding transcriptional…
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…
We consider evolution of a large population, where fitness of each organism is defined by many phenotypical traits. These traits result from expression of many genes. We propose a new model of gene regulation, where gene expression is…
Epigenetic modifications of histones crucially affect the eukaryotic gene activity, while the epigenetic histone state is largely determined by the binding of specific factors such as the transcription factors (TFs) to DNA. Here, the way…
We study theoretically the in vitro evolution of a DNA sequence by binding to a transcription factor. Using a simple model of protein-DNA binding and available binding constants for the Mnt protein, we perform large-scale, realistic…
The transcription of DNA into mRNA is initiated and aided by a number of transcription factors (TFs), proteins with DNA-binding regions that attach themselves to binding sites in the DNA (transcription factor binding sites, TFBSs). As it…
Genetic interactions can strongly influence the fitness effects of individual mutations, yet the impact of these epistatic interactions on evolutionary dynamics remains poorly understood. Here we investigate the evolutionary role of…
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…
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…
Single-molecule force spectroscopy has opened a new field of research in molecular biophysics and biochemistry. Pulling experiments on individual proteins permit us to monitor conformational transitions with high temporal resolution and…
Transcriptional activity has been shown to relate to the organization of chromosomes in the eukaryotic nucleus and in the bacterial nucleoid. In particular, highly transcribed genes, RNA polymerases and transcription factors gather into…
Regulatory networks consist of interacting molecules with a high degree of mutual chemical specificity. How can these molecules evolve when their function depends on maintenance of interactions with cognate partners and simultaneous…
Genotypic fitness landscapes are constructed by assessing the fitness of all possible combinations of a given number of mutations. In the last years, several experimental fitness landscapes have been completely resolved. As fitness…
Genotype-to-phenotype maps and the related fitness landscapes that include epistatic interactions are difficult to measure because of their high dimensional structure. Here we construct such a map using the recently collected corpora of…