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Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development

De novo establishment of DNA methylation is accomplished by DNMT3A and DNMT3B. Here, we analyze de novo DNA methylation in mouse embryonic fibroblasts (2i-MEFs) derived from DNA-hypomethylated 2i/L ES cells with genetic ablation of Dnmt3a or Dnmt3b. We identify 355 and 333 uniquely unmethylated genes in Dnmt3a and Dnmt3b knockout (KO) 2i-MEFs, respectively. We find that Dnmt3a is exclusively required for de novo methylation at both TSS regions and gene bodies of Polycomb group (PcG) target developmental genes, while Dnmt3b has a dominant role on the X chromosome. Consistent with this, tissue-specific DNA methylation at PcG target genes is substantially reduced in Dnmt3a KO embryos. Finally, we find that human patients with DNMT3 mutations exhibit reduced DNA methylation at regions that are hypomethylated in Dnmt3 KO 2i-MEFs. In conclusion, here we report a set of unique de novo DNA methylation target sites for both DNMT3 enzymes during mammalian development that overlap with hypomethylated sites in human patients

Assessing environmental pollution in birds: a new methodological approach for interpreting bioaccumulation of trace elements in feather shafts using geochemical sediment data

Environmental trace element composition can have an important impact on ecosystem and population health as well individual fitness. Therefore, carefully assessing bioaccumulation of trace elements is central to studies investigating the ecological impact of pollution. Colonial birds are important bioindicators since non-invasive sampling can easily be achieved through sampling of chick feathers, which controls for some confounding factors of variability (age and environmental heterogeneity). However, an additional confounding factor, external contamination (ExCo), which remains even after washing feathers, has frequently been overlooked in the literature. We developed a new method to reliably interpret bioaccumulation of 10 trace elements (As, Cd, Cr, Cu, Hg, Ni, Pb, Se, Sn and Zn) in feathers using chicks of a colonial species: the Greater Flamingo, Phoenicopterus roseus. First, only shafts were used to remove ExCo retained in vanes. Secondly, we applied a thorough washing procedure. Thirdly, we applied a new analytical method to control for ExCo, which assumes that ExCo is mainly due to adhered sediment particles and that the relative concentration of each trace element will be similar to the sediment geochemical composition of sampling sites. We validated this new methodology by comparing trace element composition and particle composition (by scanning electron microscopy and mass spectrometry) of washed and unwashed feathers. The washing procedure removed >99% of K indicating that most of the ExCo from salt was removed. Scanning electron microscopy and mass spectrometry revealed that some sediment particles remained after washing, especially clays which are likely to severely bias bioaccumulation interpretation. We successfully controlled for ExCo by calculating the ratio of ExCo due to sediment using the geochemical fingerprint of sediment samples. Our methodology leads to conservative estimates of bioaccumulation for As, Cd, Cr, Cu, Hg, Ni, Pb, Se, Sn and Zn. We have validated a new more reliable method of analysing trace element concentrations in feathers, which effectively controls for ExCo, if geochemical sediment data can be meaningfully compared to ExCo of feathers. We have demonstrated that overlooking ExCo leads to potentially erroneous conclusions, and we urge that the method applied in this study be considered in future studies.Peer Reviewe

REE, Uranium (U) and Thorium (Th) contents in Betula pendula leaf growing around Komsomolsk gold concentration plant tailing (Kemerovo region, Western Siberia, Russia)

The article deals with the research findings of peculiarities of REE, Uranium and Thorium distribution in the territory surrounding the tailing of former Komsomolsk gold concentration plant according to the data from Betula pendula leaf testing. In the leaf element composition the slight deficiency of MREE and substantial excess of HREE are presented. In the nearest impacted area around the tailing, La, Yb, U and Th content, and Th/U ratio are lower than in the distant buffer area. It is shown, that value of Th/U ratio and REE can be an indicator for geochemical transformations of technogenic landscapes in mining districts. The results of the research can be used for biomonitoring of the territory around the tailing

Ising Universality in Three Dimensions: A Monte Carlo Study

We investigate three Ising models on the simple cubic lattice by means of Monte Carlo methods and finite-size scaling. These models are the spin-1/2 Ising model with nearest-neighbor interactions, a spin-1/2 model with nearest-neighbor and third-neighbor interactions, and a spin-1 model with nearest-neighbor interactions. The results are in accurate agreement with the hypothesis of universality. Analysis of the finite-size scaling behavior reveals corrections beyond those caused by the leading irrelevant scaling field. We find that the correction-to-scaling amplitudes are strongly dependent on the introduction of further-neighbor interactions or a third spin state. In a spin-1 Ising model, these corrections appear to be very small. This is very helpful for the determination of the universal constants of the Ising model. The renormalization exponents of the Ising model are determined as y_t = 1.587 (2), y_h = 2.4815 (15) and y_i = -0.82 (6). The universal ratio Q = ^2/ is equal to 0.6233 (4) for periodic systems with cubic symmetry. The critical point of the nearest-neighbor spin-1/2 model is K_c=0.2216546 (10).Comment: 25 pages, uuencoded compressed PostScript file (to appear in Journal of Physics A

Salerno's model of DNA reanalysed: could solitons have biological significance?

We investigate the sequence-dependent behaviour of localised excitations in a toy, nonlinear model of DNA base-pair opening originally proposed by Salerno. Specifically we ask whether ``breather'' solitons could play a role in the facilitated location of promoters by RNA polymerase. In an effective potential formalism, we find excellent correlation between potential minima and {\em Escherichia coli} promoter recognition sites in the T7 bacteriophage genome. Evidence for a similar relationship between phage promoters and downstream coding regions is found and alternative reasons for links between AT richness and transcriptionally-significant sites are discussed. Consideration of the soliton energy of translocation provides a novel dynamical picture of sliding: steep potential gradients correspond to deterministic motion, while ``flat'' regions, corresponding to homogeneous AT or GC content, are governed by random, thermal motion. Finally we demonstrate an interesting equivalence between planar, breather solitons and the helical motion of a sliding protein ``particle'' about a bent DNA axis.Comment: Latex file 20 pages, 5 figures. Manuscript of paper to appear in J. Biol. Phys., accepted 02/09/0

Arsenic distribution and speciation in the fronds of the hyperaccumulator Pteris vittata

Pteris vittata is the first plant reported to be a hyperaccumulator of arsenic (As), and little is known about the mechanisms of As hyperaccumulation in this plant. Arsenic distribution at the whole plant (fronds) and cellular level was investigated using chemical analyses and energy dispersive X-ray microanalyses (EDXA). Speciation of As in the fronds was determined using X-ray absorption near edge spectroscopy (XANES) analyses. The majority of As was found in the pinnae (96% of total As). The concentration of As in pinnae decreased from the base to the apex of the fronds. Arsenic concentrations in spores and midribs were much lower than in the pinnae. EDXA analyses revealed that As was compartmentalized mainly in the upper and lower epidermal cells, probably in the vacuoles. The distribution pattern of potassium was similar to As, whereas other elements (Ca, Cl, K, Mg, P and S) were distributed differently. XANES analyses showed that approximately 75% of the As in fronds was present in the As(III) oxidation state and the remaining as As(V)