46 research outputs found
Quantitative test of the barrier nucleosome model for statistical positioning of nucleosomes up- and downstream of transcription start sites
The positions of nucleosomes in eukaryotic genomes determine which parts of
the DNA sequence are readily accessible for regulatory proteins and which are
not. Genome-wide maps of nucleosome positions have revealed a salient pattern
around transcription start sites, involving a nucleosome-free region (NFR)
flanked by a pronounced periodic pattern in the average nucleosome density.
While the periodic pattern clearly reflects well-positioned nucleosomes, the
positioning mechanism is less clear. A recent experimental study by Mavrich et
al. argued that the pattern observed in S. cerevisiae is qualitatively
consistent with a `barrier nucleosome model', in which the oscillatory pattern
is created by the statistical positioning mechanism of Kornberg and Stryer. On
the other hand, there is clear evidence for intrinsic sequence preferences of
nucleosomes, and it is unclear to what extent these sequence preferences affect
the observed pattern. To test the barrier nucleosome model, we quantitatively
analyze yeast nucleosome positioning data both up- and downstream from NFRs.
Our analysis is based on the Tonks model of statistical physics which
quantifies the interplay between the excluded-volume interaction of nucleosomes
and their positional entropy. We find that although the typical patterns on the
two sides of the NFR are different, they are both quantitatively described by
the same physical model, with the same parameters, but different boundary
conditions. The inferred boundary conditions suggest that the first nucleosome
downstream from the NFR (the +1 nucleosome) is typically directly positioned
while the first nucleosome upstream is statistically positioned via a
nucleosome-repelling DNA region. These boundary conditions, which can be
locally encoded into the genome sequence, significantly shape the statistical
distribution of nucleosomes over a range of up to ~1000 bp to each side.Comment: includes supporting materia
Inferring time-derivatives including cell growth rates using Gaussian processes
Often the time derivative of a measured variable is of as much interest as the variable itself. For a growing population of biological cells, for example, the population's growth rate is typically more important than its size. Here we introduce a non-parametric method to infer first and second time derivatives as a function of time from time-series data. Our approach is based on Gaussian processes and applies to a wide range of data. In tests, the method is at least as accurate as others, but has several advantages: it estimates errors both in the inference and in any summary statistics, such as lag times, and allows interpolation with the corresponding error estimation. As illustrations, we infer growth rates of microbial cells, the rate of assembly of an amyloid fibril and both the speed and acceleration of two separating spindle pole bodies. Our algorithm should thus be broadly applicable
CC9 Livestock-Associated Staphylococcus aureus Emerges in Bloodstream Infections in French Patients Unconnected With Animal Farming
We report 4 bloodstream infections associated with CC9 agr type II Staphylococcus aureus in individuals without animal exposure. We demonstrate, by microarray analysis, the presence of egc cluster, fnbA, cap operon, lukS, set2, set12, splE, splD, sak, epiD, and can, genomic features associated with a high virulence potential in human
Mechanics of the IL2RA Gene Activation Revealed by Modeling and Atomic Force Microscopy
Transcription implies recruitment of RNA polymerase II and transcription factors (TFs) by DNA melting near transcription start site (TSS). Combining atomic force microscopy and computer modeling, we investigate the structural and dynamical properties of the IL2RA promoter and identify an intrinsically negative supercoil in the PRRII region (containing Elf-1 and HMGA1 binding sites), located upstream of a curved DNA region encompassing TSS. Conformational changes, evidenced by time-lapse studies, result in the progressive positioning of curvature apex towards the TSS, likely facilitating local DNA melting. In vitro assays confirm specific binding of the General Transcription Factors (GTFs) TBP and TFIIB over TATA-TSS position, where an inhibitory nucleosome prevented preinitiation complex (PIC) formation and uncontrolled DNA melting. These findings represent a substantial advance showing, first, that the structural properties of the IL2RA promoter are encoded in the DNA sequence and second, that during the initiation process DNA conformation is dynamic and not static
Nucleosomes in gene regulation: theoretical approaches
This work reviews current theoretical approaches of biophysics and
bioinformatics for the description of nucleosome arrangements in chromatin and
transcription factor binding to nucleosomal organized DNA. The role of
nucleosomes in gene regulation is discussed from molecular-mechanistic and
biological point of view. In addition to classical problems of this field,
actual questions of epigenetic regulation are discussed. The authors selected
for discussion what seem to be the most interesting concepts and hypotheses.
Mathematical approaches are described in a simplified language to attract
attention to the most important directions of this field
Ethanol potentiates the genotoxicity of the food-derived mammary carcinogen PhIP in human estrogen receptor-positive mammary cells: mechanistic support for lifestyle factors (cooked red meat and ethanol) associated with mammary cancer
Le logiciel PEGASE et la gestion des eaux
PEGASE software has been designed to optimize water management in a river basin. The parameter defining the operational procedures of the control works can be optimized by minimizing an objective function (representing the cost of inundations, low flow water shortages, quality shortfalls and other inadequacies). This objective function is estimated from the simulation of the catchment behaviour on long historical series of hydro/meteorological data.Thus the software includes two main parts :- A conceptual simulation module of the river catchment including all the hydrological processes : surface runoff, ground flow, river flow, control structures operation, etc ...- An optimization module.The software has been designed for application on the Seine river uptream of Paris, but it may be easily adapted to a lot of situations in view to improve the management of water resources. / Le logiciel PEGASE a été réalisé pour optimiser la gestion des eaux de rivière. Les paramètres qui définissent les procédures de gestion peuvent être optimisées en minimisant une fonction objectif (représentant le coût des inondations ou des étiages, des baisses de qualité de l'eau, etc .). Cette fonction objectif est estimée via une simulation numérique du comportement du réseau à partir de longues séries de données hydro-météorologiques. Le logiciel est divisé en deux parties : - un module de simulation du réseau hydraulique comportant tous les processus hydrologiques : ruissellement de surface, écoulement souterrain, écoulement en rivière, règles de gestion, etc . - un module d'optimisation. Ce logiciel a été réalisé en vue d'une application au bassin de la Seine à l'amont de Paris, mais il peut aisément être adapté à toutes sortes de situations en vue d'améliorer la gestion de la ressource en ea
Miniaturized checkerboard assays to measure antibiotic interactions
Drugs may have synergistic or antagonistic interactions when combined. Checkerboard assays, where two drugs are combined in many doses, allow sensitive measurement of drug interactions. Here, we describe a protocol to measure the pairwise interactions among three antibiotics, in duplicate, in 5 days, using only two 96-well microplates and standard laboratory equipment
Nucleosome positioning by genomic excluding-energy barriers
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