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Volume 515 Issue 7527, 20 November 2014

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

Editorial

  • The International Council for Science needs to define its mission and show its members that it is worth their membership fees.

    Editorial

    Advertisement

  • Italy’s curators must band together to preserve their valuable collections.

    Editorial
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World View

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Research Highlights

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Social Selection

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Seven Days

  • 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.

    Seven Days
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News

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Correction

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News

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News Feature

  • Every year, the US government gives research institutions billions of dollars towards infrastructure and administrative support. A Nature investigation reveals who is benefiting most.

    • Heidi Ledford
    News Feature
  • The International Centre for Theoretical Physics was set up to seed science in the developing world; 100,000 researchers later, it is still growing.

    • Katia Moskvitch
    News Feature
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Comment

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Books & Arts

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Correspondence

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Obituary

  • Neuroscientist and psychiatrist who linked birdsong and human speech.

    • Thomas R. Insel
    • Story Landis
    Obituary
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News & Views

  • 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

    • Piero Carninci
    News & Views
  • 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

    • Sandip A. Shelke
    • Joseph A. Piccirilli
    News & Views
  • 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

    • Philippe Ghosez
    • Jean-Marc Triscone
    News & Views
  • 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

    • Luke A. J. O'Neill
    News & Views
  • 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

    • Natasha MacBean
    • Philippe Peylin

    Special:

    News & Views
  • 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

    • María C. Martí
    • Alex A. R. Webb
    News & Views
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Article

  • 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.

    • Feng Yue
    • Yong Cheng
    • Bing Ren
    Article Open Access
  • 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.

    • Yong Cheng
    • Zhihai Ma
    • Michael P. Snyder
    Article Open Access
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Letter

  • 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.

    • Deepak Venkateshvaran
    • Mark Nikolka
    • Henning Sirringhaus
    Letter
  • 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.

    • Yue-Jin Liu
    • Hui Xu
    • Jin-Quan Yu
    Letter
  • 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.

    • Benjamin D. Pope
    • Tyrone Ryba
    • David M. Gilbert
    Letter Open Access
  • 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.

    • Brian Tilston Smith
    • John E. McCormack
    • Robb T. Brumfield
    Letter
  • 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.

    • Fabrizio Sergio
    • Alessandro Tanferna
    • Fernando Hiraldo
    Letter
  • 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.

    • Zhexing Wen
    • Ha Nam Nguyen
    • Guo-li Ming
    Letter
  • 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.

    • Motomu Endo
    • Hanako Shimizu
    • Steve A. Kay
    Letter
  • 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.

    • Ansel Hsiao
    • A. M. Shamsir Ahmed
    • Jeffrey I. Gordon
    Letter
  • 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.

    • Katherine E. Wright
    • Kathryn A. Hjerrild
    • Matthew K. Higgins
    Letter
  • 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.

    • Edward T. Chouchani
    • Victoria R. Pell
    • Michael P. Murphy
    Letter
  • 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.

    • Havva Keskin
    • Ying Shen
    • Francesca Storici
    Letter
  • 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.

    • Jonathan T. Sczepanski
    • Gerald F. Joyce
    Letter
  • 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.

    • Chao Yan
    • Degang Liu
    • Dan Theodorescu
    Letter
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Feature

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Q&A

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Career Brief

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Futures

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Outlook

    • Brian Owens
    Outlook
  • 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.

    • David Holmes
    Outlook
  • Spending time in the sun is a major risk factor for melanoma, but the relationship is not as straightforward as it seems.

    • Cassandra Willyard
    Outlook
  • The United States and other nations should follow Germany in routine skin screening, say Susan M. Swetter and Alan C. Geller.

    • Susan M. Swetter
    • Alan C. Geller
    Outlook
  • People with advanced melanoma are living longer thanks to treatments that target cancerous cells or encourage the immune system to wipe out the tumour.

    • Hannah Hoag
    Outlook
  • 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.

    • Sujata Gupta
    Outlook
  • A tablet that protects against sunburn is an attractive idea, but the science is patchy.

    • Erin Biba
    Outlook
  • The United States does not have access to the latest sunscreens. The Sunscreen Innovation Act could set that right, says Michael J. Werner.

    • Michael J. Werner
    Outlook
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Nature Outlook

  • 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.

    Nature Outlook
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