Long-range effects of histone point mutations on DNA remodeling revealed from computational analyses of SIN-mutant nucleosome structures

The packaging of DNA into nucleosomes impedes the binding and access of molecules involved in its processing. The SWI/SNF multi-protein assembly, found in yeast, is one of many regulatory factors that stimulate the remodeling of DNA required for its transcription. Amino-acid point mutations in histones H3 or H4 partially bypass the requirement of the SWI/SNF complex in this system. The mechanisms underlying the observed remodeling, however, are difficult to discern from the crystal structures of nucleosomes bearing these so-called SIN (SWI/SNF INdependent) mutations. Here, we report detailed analyses of the conformations and interactions of the histones and DNA in these assemblies. We find that the loss of direct protein–DNA contacts near point-mutation sites, reported previously, is coupled to unexpected additional long-range effects, i.e. loss of intermolecular contacts and accompanying DNA conformational changes at sequentially and spatially distant sites. The SIN mutations seemingly transmit information relevant to DNA binding across the nucleosome. The energetic cost of deforming the DNA to the states found in the SIN-mutant structures helps to distinguish the mutants that show phenotypes in yeast from those that do not. Models incorporating these deformed dimer steps suggest ways that nucleosomal DNA may be remodeled during its biological processing

The activity of the histone chaperone yeast Asf1 in the assembly and disassembly of histone H3/H4–DNA complexes

The deposition of the histones H3/H4 onto DNA to give the tetrasome intermediate and the displacement of H3/H4 from DNA are thought to be the first and the last steps in nucleosome assembly and disassembly, respectively. Anti-silencing function 1 (Asf1) is a chaperone of the H3/H4 dimer that functions in both of these processes. However, little is known about the thermodynamics of chaperone–histone interactions or the direct role of Asf1 in the formation or disassembly of histone–DNA complexes. Here, we show that Saccharomyces cerevisiae Asf1 shields H3/H4 from unfavorable DNA interactions and aids the formation of favorable histone–DNA interactions through the formation of disomes. However, Asf1 was unable to disengage histones from DNA for tetrasomes formed with H3/H4 and strong nucleosome positioning DNA sequences or tetrasomes weakened by mutant (H3K56Q/H4) histones or non-positioning DNA sequences. Furthermore, Asf1 did not associate with preformed tetrasomes. These results are consistent with the measured affinity of Asf1 for H3/H4 dimers of 2.5 nM, which is weaker than the association of H3/H4 for DNA. These studies support a mechanism by which Asf1 aids H3/H4 deposition onto DNA but suggest that additional factors or post-translational modifications are required for Asf1 to remove H3/H4 from tetrasome intermediates in chromatin

Non linear properties of dense PIN-PT ceramics

International audienceNonlinear measurements of dense 63PbIn1/2Nb1/2- 37PbTiO3 (PIN-37PT) piezoceramics, was recorded at 1 kHz and at resonance under driven AC electric fields and axial static pressure. Influence of donor or softener (Mg, Nb) and acceptor or hardener (Mn) was investigated. Dependence of the real and imaginary parts of the dielectric constant on electric field was compared with PZT hard ceramics and PMN-PT soft ceramics. The mechanical nonlinear behavior of piezoelectric ceramics, characterized by two coefficients (α and β), was measured according to the CENELEC European Standards EN5034-3. The new mechanical nonlinear coefficient β measures the compliance variation. The α and β coefficients of PIN-37PT ceramics, 0.95×106 and 3.8×106, are larger than that hard PZT8 (0.03×106 and 0.3×10 5). © 2009 Materials Research Society

Grain size effect on electromechanical properties and non-linear response of dense nano and microstructured PIN-PT ceramics

International audienceNanopowders of 0.63Pb(In1/2Nb1/2)O-3-0.37PbTiO(3) were synthesized by solid state reaction using the continuous attrition milling followed by high-energy ball milling techniques in air at room temperature. After milling for 8 h nanopowders of 20-30 nm grain size are obtained. Sintering by hot pressing of PIN-37PT green pellets leads to dense ceramics with average grain size varying from 100 nm to 1 mu m. The dielectric and piezoelectric properties of PIN-37PT nanostructured ceramics with grain size bigger than about 160 nm remain roughly unchanged and comparable to those of microstructured ceramics. In addition, the stability of the permittivity and dielectric losses under high ac electric field grows when the grain size decreases. The material becomes less non-linear with decreasing grain size. This result is attractive for acoustic transducer applications

Thermal state of a conical antenna cooled by means of nanofluid saturated porous media

Thermal state of a conical antenna used for big data transfer was determined in this work. Its cooling is provided through porous media saturated with water-based copper nanofluid (NF) whose volume fraction varies in the 0% (pure water)-10% range. Otherwise, the ratio between the thermal conductivity of the highly porous material and that of the fluid base (water) varies between 4 and 41.2. The solution is obtained by means of 3D numerical approach based on the volume control method using the SIMPLE algorithm in the large 3.32×105-6.74×107 Rayleigh number range. The average temperature of the antenna can be determined with the correlation proposed in this work for any combination of the thermal conductivity ratio, volume fraction and Rayleigh number. This new and original correlation makes it possible to determine the optimal values of these three influencing parameters to ensure the correct antenna's operation. © 2022 World Scientific Publishing Company

P1-03: A multi-omics strategy to depict and compare the hepatotoxic mechanisms of chlordecone and its metabolite chlordecol

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A multi-omics strategy to depict and compare the hepatotoxic mechanisms of chlordecone and its metabolite chlordecol

International audienc

Histone H3-variant Cse4-induced positive DNA supercoiling in the yeast plasmid has implications for a plasmid origin of a chromosome centromere

The Saccharomyces cerevisiae 2-μm plasmid is a multicopy selfish genome that resides in the nucleus. The genetic organization of the plasmid is optimized for stable, high-copy propagation in host-cell populations. The plasmid's partitioning system poaches host factors, including the centromere-specific histone H3-variant Cse4 and the cohesin complex, enabling replicated plasmid copies to segregate equally in a chromosome-coupled fashion. We have characterized the in vivo chromatin topology of the plasmid partitioning locus STB in its Cse4-associated and Cse4-nonassociated states. We find that the occupancy of Cse4 at STB induces positive DNA supercoiling, with a linking difference (ΔLk) contribution estimated between +1 and +2 units. One plausible explanation for this contrary topology is the presence of a specialized Cse4-containing nucleosome with a right-handed DNA writhe at a functional STB, contrasted by a standard histone H3-containing nucleosome with a left-handed DNA writhe at a nonfunctional STB. The similarities between STB and centromere in their nucleosome signature and DNA topology would be consistent with the potential origin of the unusual point centromere of budding yeast chromosomes from the partitioning locus of an ancestral plasmid

Nucleosomes can invade DNA territories occupied by their neighbors

Nucleosomes are the fundamental subunits of eukaryotic chromatin. They are not static entities, but can undergo a number of dynamic transitions including spontaneous repositioning along DNA. Since nucleosomes are spaced close together within genomes it is likely that on occasion they approach each other and or collide. Here we have used a dinucleosomal model system to show that the 147bp DNA territories of two nucleosomes can overlap extensively. In the situation of an overlap by 44 bp or 54 bp one histone dimer is lost and the resulting complex can condense to form a compact single particle. We propose a pathway in which adjacent nucleosomes promote DNA unraveling as they approach each other and that this permits their 147bp territories to overlap. These may represent early steps in a pathway for nucleosome removal via collision. In eukaryotic cells genomic DNA exists in the form of a nucleo-protein complex called chromatin 1. The packaging of the genomic DNA imposes a hindrance to most DNA-dependent processes including DNA replication, repair and mRNA transcription. This implies an important role for chromatin structure in the control of many nuclear functions 2,3. The first step in the packaging hierarchy of chromatin is the formation of a nucleosom