Genome-wide profiling of nucleosome sensitivity and chromatin accessibility in Drosophila melanogaster

textabstractNucleosomal DNA is thought to be generally inaccessible to DNA-binding factors, such as micrococcal nuclease (MNase). Here, we digest Drosophila chromatin with high and low concentrations of MNase to reveal two distinct nucleosome types: MNasesensitive and MNase-resistant. MNase-resistant nucleosomes assemble on sequences depleted of A/T and enriched in G/C-containing dinucleotides, whereas MNase-sensitive nucleosomes form on A/Trich sequences found at transcription start and termination sites, enhancers and DNase I hypersensitive sites. Estimates of nucleosome formation energies indicate that MNase-sensitive nucleosomes tend to be less stable than MNase-resistant ones. Strikingly, a decrease in cell growth temperature of about 10?C makes MNase-sensitive nucleosomes less accessible, suggesting that observed variations in MNase sensitivity are related to either thermal fluctuations of chromatin fibers or the activity of enzymatic machinery. In the vicinity of active genes and DNase I hypersensitive sites nucleosomes are organized into periodic arrays, likely due to 'phasing' off potential barriers formed by DNA-bound factors or by nucleosomes anchored to their positions through external interactions. The latter idea is substantiated by our biophysical model of nucleosome positioning and energetics, which predicts that nucleosomes immediately downstream of transcription start sites are anchored and recapitulates nucleosome phasing at active genes significantly better than sequencedependent models

Mating with immunised male mice affects the phenotype of adult progeny

The life-history theory suggests that parental experience of the environment is passed to offspring, which allows them to adapt to prevailing conditions. This idea is supported from the mother's side, but to a much less extent from the father's side. Here, we investigated the effect of immunising fathers on pre- and neonatal development and on immune and neuroendocrine phenotypes of their offspring in C57BL/6J mice. Nine days before mating, fathers were intraperitoneally injected with the immunogenic protein keyhole limpet hemocyanin (KLH). Females mated with immunised males had less pre-weaning mortality of newborns compared to those mated with control males. Although the antibody response to KLH was similar for the male offspring of control and immunised fathers, the mass indexes of their main immune organs and their androgen response differed significantly. The mass indexes of the thymus and spleen in adult male offspring of immunised fathers were higher compared with the control offspring. The plasma testosterone levels were significantly decreased after KLH administration in the male offspring of control but not of immunised fathers. This was correlated with changes in sperm average path and straight-line velocities. Finally, excitatory neurotransmitters prevailed over inhibitory ones in the amygdala of the progeny of immunised fathers, while in control offspring, the opposite occurred. This is indicative of complex behavioural changes in the offspring of immunised fathers, including sexual ones. Therefore, the paternal experience of foreign antigens modulates the immune and neuroendocrine systems of their progeny, suggesting possible survival and reproductive adaptations to parasitic pressure

COMPEL: a database on composite regulatory elements providing combinatorial transcriptional regulation

COMPEL is a database on composite regulatory elements, the basic structures of combinatorial regulation. Composite regulatory elements contain two closely situated binding sites for distinct transcription factors and represent minimal functional units providing combinatorial transcriptional regulation. Both specific factor–DNA and factor–factor interactions contribute to the function of composite elements (CEs). Information about the structure of known CEs and specific gene regulation achieved through such CEs appears to be extremely useful for promoter prediction, for gene function prediction and for applied gene engineering as well. The structure of the relational model of COMPEL is determined by the concept of molecular structure and regulatory role of CEs. Based on the set of a particular CE, a program has been developed for searching potential CEs in gene regulatory regions. WWW search and browse routines were developed for COMPEL release 3.0. The COMPEL database equipped with the search and browse tools is available at http://compel.bionet.nsc.ru/ . The program for prediction of potential CEs of NFAT type is available at http://compel.bionet.nsc.ru/FunSite.html and http://transfac.gbf.de/dbsearch/funsitep/s_comp.htm

Nanoparticles Associate with Intrinsically Disordered RNA-Binding Proteins

Nanoparticles are capable of penetrating cells, but little is known about the way they interact with intracellular proteome. Here we show that inorganic nanoparticles associate with low-complexity, intrinsically disordered proteins from HeLa cytosolic protein extracts in nondenaturing <i>in vitro</i> nanoparticle pull-down assays. Intrinsic protein disorder associates with structural mobility, suggesting that side-chain flexibility plays an important role in the driving of a protein to nanoparticle absorption. Disordered protein domains are often found in a diverse group of RNA-binding proteins. Consequently, the nanoparticle-associated proteomes were enriched in subunits of RNA-processing protein complexes. In turn, this indicates that within a cell, nanoparticles might interfere with protein synthesis triggering a range of cellular responses