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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…
Current models for the folding of the human genome see a hierarchy stretching down from chromosome territories, through A/B compartments and TADs (topologically-associating domains), to contact domains stabilized by cohesin and CTCF.…
We use Brownian dynamics simulations to study the formation of chromatin loops through diffusive sliding of slip-link-like proteins, mimicking the behaviour of cohesin molecules. We recently proposed that diffusive sliding is sufficient to…
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…
Condensation of hundreds of mega-base-pair-long human chromosomes in a small nuclear volume is a spectacular phenomenon. This process is driven by the formation of chromosome loops. ATP consuming motor, condensin, interacts with chromatin…
Chromatin loop extrusion is a popular model for the formation of CTCF loops and topological domains. Recent HiC data have revealed a strong bias in favour of a particular arrangement of the CTCF binding motifs that stabilize loops, and…
We present a study investigating the role of mitochondrial variability in generating noise in eukaryotic cells. Noise in cellular physiology plays an important role in many fundamental cellular processes, including transcription,…
Noise in gene expression, either due to inherent stochasticity or to varying inter- and intracellular environment, can generate significant cell-to-cell variability of protein levels in clonal populations. We present a theoretical…
We propose a model for the formation of chromatin loops based on the diffusive sliding of a DNA-bound factor which can dimerise to form a molecular slip-link. Our slip-links mimic the behaviour of cohesin-like molecules, which, along with…
Chromatin loop extrusion by Structural Maintenance of Chromosome (SMC) complexes is thought to underlie intermediate-scale chromatin organization inside cells. Motivated by a number of experiments suggesting that nucleosomes may block loop…
Even under constant external conditions, the expression levels of genes fluctuate. Much emphasis has been placed on the components of this noise that are due to randomness in transcription and translation; here we analyze the role of noise…
Transcription is a fundamental cellular process, and the first step of gene expression. In human cells, it depends on the binding to chromatin of various proteins, including RNA polymerases and numerous transcription factors (TFs).…
Recently, several studies have investigated the transcription process associated to specific genetic regulatory networks. In this work, we present a stochastic approach for analyzing the dynamics and effect of negative feedback loops (FBL)…
Active loop extrusion - the process of formation of dynamically growing chromatin loops due to the motor activity of DNA-binding protein complexes - is firmly established mechanism responsible for chromatin spatial organization at different…
Coupling the control of expression stochasticity (noise) to the ability of expression change (plasticity) can alter gene function and influence adaptation. A number of factors, such as transcription re-initiation, strong chromatin…
The spreading and regulation of epigenetic marks on chromosomes is crucial to establish and maintain cellular identity. Nonetheless, the dynamical mechanism leading to the establishment and maintenance of a given, cell-line specific,…
Three-dimensional (3D) chromatin structure is closely related to genome function, in particular transcription. However, the folding path of the chromatin fiber in the interphase nucleus is unknown. Here, we systematically measured the 3D…
Magnetic tweezers are used to study the mechanical response under torsion of single nucleosome arrays reconstituted on tandem repeats of 5S positioning sequences. Regular arrays are extremely resilient and can reversibly accommodate a large…
Increasing evidence suggests that chromosome folding and genetic expression are intimately connected. For example, the co-expression of a large number of genes can benefit from their spatial co-localization in the cellular space.…
Living cells provide a fluctuating, out-of-equilibrium environment in which genes must coordinate cellular function. DNA looping, which is a common means of regulating transcription, is very much a stochastic process; the loops arise from…