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The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks…
Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key…
Epistasis occurs when the effect of a mutation depends on its carrier's genetic background. Despite increasing evidence that epistasis for fitness is common, its role during evolution is contentious. Fitness landscapes, mappings of genotype…
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…
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…
Quantitative understanding of the principles regulating nucleosome occupancy on a genome-wide level is a central issue in eukaryotic genomics. Here, we address this question using budding yeast, Saccharomyces cerevisiae, as a model…
Homeostasis of protein concentrations in cells is crucial for their proper functioning, and this requires concentrations (at their steady-state levels) to be stable to fluctuations. Since gene expression is regulated by proteins such as…
A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the…
The mutation and selection of regulatory DNA sequences is presented as an ideal model system of molecular evolution where genotype, phenotype, and fitness can be explicitly and independently characterized. In this theoretical study, we…
One goal of human genetics is to understand how the information for precise and dynamic gene expression programs is encoded in the genome. The interactions of transcription factors (TFs) with DNA regulatory elements clearly play an…
Transcription factor binding sites vary in their specificity, both within and between species. Binding specificity has a strong impact on the evolution of gene expression, because it determines how easily regulatory interactions are gained…
Much of the complexity observed in gene regulation originates from cooperative protein-DNA binding. While studies of the target search of proteins for their specific binding sites on the DNA have revealed design principles for the…
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…
Recent genome-wide measurements of binding preferences of ~200 transcription regulators in the vicinity of transcription start sites in yeast, have provided a unique insight into the cis- regulatory code of a eukaryotic genome (Venters et…
Transcription factors (TFs) regulate gene expression through complex and co-operative mechanisms. While many TFs act together, the logic underlying TFs binding and their interactions is not fully understood yet. Most current approaches for…
We study theoretical ``design principles'' for transcription factor-DNA interaction in bacteria, focusing particularly on the statistical interaction of the transcription factors (TF's) with the genomic background (i.e., the genome without…
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…
Transcription factors (TFs) exert their regulatory action by binding to DNA with specific sequence preferences. However, different TFs can partially share their binding sequences due to their common evolutionary origin. This `redundancy' of…
Response time and transcription level are vital parameters of gene regulation. They depend on how fast transcription factors (TFs) find and how efficient they occupy their specific target sites. It is well known that target site search is…
Genome-wide experiments to map the DNA-binding locations of transcription-associated factors (TFs) have shown that the number of genes bound by a TF far exceeds the number of possible direct target genes. Distinguishing functional from…