Related papers: Modelling chromosome-wide target search
We study how Cas9, a central component of the CRISPR/Cas9 system, searches for a target sequence on the DNA. We propose a model that includes as key ingredients 3D diffusion, 1D sliding along the DNA, and the effect of short binding…
In many cases, transcriptional regulation involves the binding of transcription factors at sites on the DNA that are not immediately adjacent to the promoter of interest. This action at a distance is often mediated by the formation of DNA…
The diffusive arrival of transcription factors at the promoter sites on the DNA sets a lower bound on how accurately a cell can regulate its protein levels. Using results from the literature on diffusion-influenced reactions, we derive an…
The mean time required by a transcription factor (TF) or an enzyme to find a target in the nucleus is of prime importance for the initialization of transcription, gene activation or the start of DNA repair. We obtain new estimates for the…
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…
Transcription factors are proteins that regulate gene activity by activating or repressing gene transcription. A special class of transcriptional repressors operates via a short-range mechanism, making local DNA regions inaccessible to…
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…
Protein-DNA interactions are crucial for all biological processes. One of the most important fundamental aspects of these interactions is the process of protein searching and recognizing specific binding sites on DNA. A large number of…
Many fundamental biological processes are regulated by protein-DNA complexes called {\it synaptosomes}, which possess multiple interaction sites. Despite the critical importance of synaptosomes, the mechanisms of their formation remain not…
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)…
Our aim is to predict how often genic and non-genic promoters fire within a cell. We first review a parsimonious pan-genomic model for genome organization and gene regulation, where transcription rate is determined by proximity in 3D space…
We present Brownian dynamics simulations of the facilitated diffusion of a protein, modelled as a sphere with a binding site on its surface, along DNA, modelled as a semi-flexible polymer. We consider both the effect of DNA organisation in…
For most of the important processes in DNA metabolism, a protein has to reach a specific binding site on the DNA. The specific binding site may consist of just a few base pairs while the DNA is usually several millions of base pairs long.…
Protein-DNA interactions are critical for the successful functioning of all natural systems. The key role in these interactions is played by processes of protein search for specific sites on DNA. Although it has been studied for many years,…
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…
We employ the diffusing transcription factors model for numerical simulation of chromatin topology conformations and transcriptional processes of human chromatin. Simulations of a short chromatin filament reveal different possible pathways…
We study the impact of DNA coiling on the search rate of proteins moving along the DNA contour interspersed by three-dimensional (3D) bulk excursions. When the DNA is coiled proteins performing short 3D hops along a DNA segment can be…
By analyzing the spacing of genes on chromosomes, we find that transcriptional and RNA-processing regulatory sequences outside coding regions leave footprints on the distribution of intergenic distances. Using analogies between genes on…
Cells regulate fates and complex body plans using spatiotemporal signaling cascades that alter gene expression. Enhancers, short DNA sequences (50-150 base pairs), help coordinate these cascades by attracting regulatory proteins to enhance…
Proteins can locate their specific targets on DNA up to two orders of magnitude faster than the Smoluchowski three-dimensional diffusion rate. This happens due to non-specific adsorption of proteins to DNA and subsequent one-dimensional…