Related papers: Modelling chromosome-wide target search
Many cellular responses to surrounding cues require temporally concerted transcriptional regulation of multiple genes. In prokaryotic cells, a single-input-module motif with one transcription factor regulating multiple target genes can…
Timely up- or down-regulation of gene expression is crucial for cellular differentiation and function. While gene upregulation via transcriptional activators has been extensively investigated, gene silencing remains understudied, especially…
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…
A transversal topic of my research has been the development and application of computational methods for DNA sequence analysis. The methods I have been developing aim at improving our understanding of the regulation processes happening in…
Several important biological processes are initiated by the binding of a protein to a specific site on the DNA. The strategy adopted by a protein, called transcription factor (TF), for searching its specific binding site on the DNA has been…
Transcription factors are able to associate to their binding sites on DNA faster than the physical limit posed by diffusion. Such high association rates can be achieved by alternating between three-dimensional diffusion and one-dimensional…
Recognition and binding of specific sites on DNA by proteins is central for many cellular functions such as transcription, replication, and recombination. In the process of recognition, a protein rapidly searches for its specific site on a…
The formation of DNA loops by proteins and protein complexes that bind at distal DNA sites plays a central role in many cellular processes, such as transcription, recombination, and replication. Here we review the basic thermodynamic…
In computational molecular biology, gene regulatory binding sites prediction in whole genome remains a challenge for the researchers. Now a days, the genome wide regulatory binding site prediction tools required either direct pattern…
The set of regulatory interactions between genes, mediated by transcription factors, forms a species' transcriptional regulatory network (TRN). By comparing this network with measured gene expression data one can identify functional…
We present a novel framework for understanding node target search in systems organized as hierarchical networks-within-networks. Our work generalizes traditional search models on complex networks, where the mean-first passage time is…
In bacteria, regulatory proteins search for a specific DNA binding target via "facilitated diffusion": a series of rounds of 3D diffusion in the cytoplasm, and 1D linear diffusion along the DNA contour. Using large scale Brownian dynamics…
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…
We present a theoretical model of facilitated diffusion of proteins in the cell nucleus. This model, which takes into account the successive binding/unbinding events of proteins to DNA, relies on a fractal description of the chromatin which…
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…
DNA sequence alignment involves assigning short DNA reads to the most probable locations on an extensive reference genome. This process is crucial for various genomic analyses, including variant calling, transcriptomics, and epigenomics.…
Protein complexes involved in DNA mismatch repair appear to diffuse along dsDNA in order to locate a hemimethylated incision site via a dissociative mechanism. Here, we study the probability that these complexes locate a given target site…
Unbalanced translocations are among the most frequent chromosomal alterations, accounted for 30\% of all losses of heterozygosity, a major genetic event causing inactivation of tumor suppressor genes. Despite of their central role in…
It has been reported that the number of transcription factors encoded in prokaryotic genomes scales approximately quadratically with their total number of genes. We propose a conceptual explanation of this finding and illustrate it using a…
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…