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The mouse is the premier model organism in biomedical research. To gain greater insights into the shared and species-specific transcriptional and cellular regulatory programs, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. These finding are compared with the corresponding human data to confirm substantial conservation in the newly annotated potential functional sequences, and to reveal pronounced divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. The data and their analyses provide a valuable resource for research into mammalian biology and mechanisms of human diseases. This issue of Nature includes four further Mouse ENCODE papers and in News & Views, Piero Carninci considers how the mouse ENCODE datasets will contribute to our understanding of human biology and biomedicine. Cover: Kelly Krause/ Nature
The week in science: China and United States announce plans to cut emissions; European Commission scraps chief science adviser post; and pharma firm Actavis announces a US$66-billion takeover.
Every year, the US government gives research institutions billions of dollars towards infrastructure and administrative support. A Nature investigation reveals who is benefiting most.
Following on from affiliated projects in humans and model invertebrates, the Mouse ENCODE Project presents comprehensive data sets on genome regulation in this key mammalian model. See Articles p.355, p.365, p.371 & Letter p.402
An RNA enzyme has been generated that can assemble a mirror-image version of itself. The finding helps to answer a long-standing conundrum about how RNA molecules could have proliferated on prebiotic Earth. See Letter p.440
Domain walls are natural borders in ferromagnetic, ferroelectric or ferroelastic materials. It seems that they can also be reactive areas that produce crystallographic phases never before observed in bulk materials. See Letter p.379
The high levels of tissue-damaging reactive oxygen species that arise during a stroke or heart attack have been shown to be generated through the accumulation of the metabolic intermediate succinate. See Letter p.431
Evolving agricultural practices dramatically increased crop production in the twentieth century. Two studies now find that this has altered the seasonal flux of atmospheric carbon dioxide. See Letters p.394 & p.398
Techniques for isolating and analysing leaf cell types have now been developed, leading to the discovery that circadian clocks in the plant vasculature communicate with and regulate clocks in neighbouring cells. See Letter p.419
The Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types; these data were compared with those from human to confirm substantial conservation in the newly annotated potential functional sequences and to reveal pronounced divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization.
Mouse genomic footprinting reveals conservation of transcription factor (TF) recognition repertoires and trans-regulatory circuitry despite massive turnover of DNA elements that contact TFs in vivo.
As part of the mouse ENCODE project, genome-wide transcription factor (TF) occupancy repertoires and co-association patterns in mice and humans are studied; many aspects are conserved but the extent to which orthologous DNA segments are bound by TFs in mice and humans varies both among TFs and genomic location, and TF-occupied sequences whose occupancy is conserved tend to be pleiotropic and enriched for single nucleotide variants with known regulatory potential.
Blazars are quasars with a jet pointing towards Earth; analysis of archival observations of a sample of blazars reveals that jet power is larger than, and correlates with, the accretion luminosity, in agreement with numerical simulations.
The strain induced on the walls between ferroelastic domains of a thin film of terbium manganite grown on a substrate of strontium titanate can generate an unusual two-dimensional ferromagnetic phase that is yet to be produced by conventional chemical means.
Measurements and simulations of several high-mobility conjugated polymers show that their charge transport properties reflect an almost complete lack of disorder in the polymers, despite their amorphous microstructures, resulting from the resilience of the planar polymer backbone conformations to side-chain disorder.
A robust and synthetically useful method is reported that overcomes the complications associated with performing C–H functionalization reactions on heterocycles; a reactive PdX2 (X = ArCONOMe) species is generated in situ, and is directed to the appropriate C–H bond by an N-methoxy amide group.
The increase in amplitude of the atmospheric carbon dioxide cycle over the past fifty years can be attributed in part to the intensification of agriculture in the Northern Hemisphere.
Increases in agricultural productivity are shown, using production statistics and a carbon accounting model, to explain as much as a quarter of the observed increase in the seasonal amplitude of the Northern Hemisphere atmospheric carbon dioxide cycle.
A study of DNA replication timing in mouse and human cells reveals that replication domains (domains of the genome which replicate at the same time) share a correlation with topologically associating domains; these results reconcile cell-type-specific sub-nuclear compartmentalization with developmentally stable chromosome domains and offer a unified model for large scale chromosome structure and function.
Diversification of Neotropical birds is not directly linked to the Andean uplift, the major landscape change of the Neogene period; instead, most diversification is post-Neogene and species diversity is dependent on how long lineages have persisted in the landscape and how easily they disperse.
A cross-sectional study of migrating raptors aged from 1 to 27 years old shows that migratory performance gradually improves with age and is driven both by selective mortality and individual improvement, with younger birds leaving progressively earlier as they age and becoming more proficient at coping with adverse environmental conditions, such as unfavourable winds.
Generation and neural differentiation of induced pluripotent stem cells (iPS cells) from patients enables new ways to investigate the cellular pathophysiology of mental disorders; this approach was used with samples from a family with a schizophrenia pedigree and a DISC1 mutation, revealing synaptic abnormalities and large-scale transcriptional dysregulation.
A detailed analysis of Arabidopsis leaf tissues using two new versatile techniques reveals that within vasculature tissue circadian clocks have characteristics distinct from those in other tissues, and that the vasculature clocks affect circadian clock regulation in other tissues; indicating that plants, like mammals, have a dual clock system.
Recovery from cholera is characterized by a pattern of accumulation of bacterial taxa that shows similarities to the pattern of maturation of the gut microbiota in healthy children, raising the possibility that some of these taxa may be useful for ‘repair’ of the gut microbiota in individuals whose gut communities have been ‘wounded’ through a variety of insults.
Reticulocyte-binding protein homologue 5 (PfRH5) of Plasmodium falciparum, the malaria parasite, is known to be necessary for red blood cell invasion, making PfRH5 a promising vaccine candidate; here the X-ray crystallographic structure of PfRH5 in complex with basigin and with inhibitory antibodies is determined.
A metabolomics study on the ischaemic heart identifies succinate as a metabolite that drives the production of reactive oxygen species and contributes to ischaemia-reperfusion injury; pharmacological inhibition of succinate accumulation ameliorates ischaemia-reperfusion injury in a mouse model of heart attack and a rat model of stroke.
Endogenous RNA transcripts are shown to mediate recombination with yeast chromosomal DNA; as the level of RNAs in the nucleus is quite high, these results may open up new understanding of the plasticity of repair and genome instability mechanisms.
Here, a cross-chiral RNA polymerase is developed—an RNA enzyme that can catalyse the templated polymerization of activated mononucleotides that are of the opposite handedness—shedding light on how RNA-based life could have emerged.
Using a structure-based approach, small molecule inhibitors that selectively target the GTPase Ral are identified and characterized; these first-generation inhibitors will be valuable tools for elucidating the Ral signalling pathway and constitute a step towards developing Ral-specific agents for cancer therapy.
The X-ray crystal structures of two bacterial homologues of the SWEET sugar transporters are solved in two conformational states, and comparison of these states suggests that transport occurs via a ‘rocker-switch’ mechanism.
Melanoma is an aggressive cancer that normally starts in the skin. It can strike anyone but is most common in people with pale skin, and it is getting more common. By David Holmes.
People with advanced melanoma are living longer thanks to treatments that target cancerous cells or encourage the immune system to wipe out the tumour.
Melanoma is most common in light-skinned people, but it can also afflict those with darker pigment. Finding out why would help to explain the disease's origins.
Melanoma — the deadliest form of skin cancer — is on the rise in many parts of the world. But new treatments, and efforts to tell people how to prevent it, could mean we will soon gain the upper hand on the disease.