Related papers: The Functional Consequences of Variation in Transc…
Transcriptional regulation by transcription factors and post-transcriptional regulation by microRNAs constitute two major modes of regulation of gene expression. While gene expression motifs incorporating solely transcriptional regulation…
In many organisms the expression levels of each gene are controlled by the activation levels of known "Transcription Factors" (TF). A problem of considerable interest is that of estimating the "Transcription Regulation Networks" (TRN)…
We present a detailed analysis, based on the Forward Flux Sampling (FFS) simulation method, of the switching dynamics and stability of two models of genetic toggle switches, consisting of two mutually-repressing genes encoding transcription…
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…
We study the effects of multiple binding sites in the promoter of a genetic oscillator. We evaluate the regulatory function of a promoter with multiple binding sites in the absence of cooperative binding, and consider different hypotheses…
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…
Gene expression is a central process to any form of life. It involves multiple temporal and functional scales that extend from specific protein-DNA interactions to the coordinated regulation of multiple genes in response to intracellular…
Recent data support the notion that a group of key transcriptional regulators involved in tumorigenesis, including MYC, p53, E2F1, and BMI1, share an intriguing capacity to simultaneously regulate metabolism and cell cycle. Here, we show…
Many transcription factors bind to DNA with a remarkable lack of specificity, so that regulatory binding sites compete with an enormous number of non-regulatory 'decoy' sites. For an auto-regulated gene, we show decoy sites decrease noise…
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)…
Gene Regulatory Networks (GRNs) consisting of combinations of transcription factors (TFs) and their cis promoters are assumed to be sufficient to direct the development of organisms. Mutations in GRNs are assumed to be the primary drivers…
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…
It is well known that, under suitable conditions, microRNAs are able to fine tune the relative concentration of their targets to any desired value. We show that this function is particularly effective when one of the targets is a…
Gene expression is a complex and quantitative trait that is influenced by both genetic and non-genetic regulators including environmental factors. Evaluating the contribution of environment to gene expression regulation and identifying…
Variability in drug efficacy and adverse effects are observed in clinical practice. While the extent of genetic variability in classical pharmacokinetic genes is rather well understood, the role of genetic variation in drug targets is…
The promise of discovering a functional blueprint of a cellular system from large-scale and high-throughput sequence and experimental data is predicated on the belief that the same top-down investigative approach that proved successful in…
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…
DNA looping participates in transcriptional regulation, for instance, by allowing distal binding sites to act synergistically. Here we study this process and compare different regulatory mechanisms based on repression with and without…
Gene expression data is essential for understanding how genes are regulated and interact within biological systems, providing insights into disease pathways and potential therapeutic targets. Gene knockout has proven to be a fundamental…
Strong experimental and theoretical evidence shows that transcription factors and other specific DNA-binding proteins find their sites using a two-mode search: alternating between 3D diffusion through the cell and 1D sliding along the DNA.…