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Volume 500 Issue 7463, 22 August 2013

This plot shows the dynamic methylation landscape of the human genome, where the x axis (left) corresponds to the maximal observed methylation change across 24 human cell and tissue types, y is the median total methylation and z is the density of CpG dinucleotides. The methylation of cytosine, usually at CpGs, is a common feature of epigenetic regulation of gene expression. Most cell types have relatively stable CpG dinucleotide methylation patterns and our understanding of which CpGs participate in genomic regulation is limited. Here, Meissner and colleagues analyse whole-genome bisulphite sequencing data sets across diverse human cell and tissue types and find that only about 22% of CpGs change their methylation state across these. Most of these CpGs are located at putative gene regulatory elements, particularly enhancers and transcription-factor-binding sites. In addition to further clarifying the distribution of DNA methylation, these selected regions with dynamic DNA methylation patterns could help guide more efficient genomic approaches to focus on informative regions, as well as help define regulatory elements. Cover: Bang Wong and Michael Ziller.


  • Editorial |

    Even when conducting clinical trials to study widely used therapies, researchers must ensure that they disclose the full risks to patients.

World View

  • World View |

    Government reforms to the Russian Academy of Sciences have met with controversy, but some form of change is needed, argues Mikhail Gelfand.

    • Mikhail Gelfand

Research Highlights

Seven Days

  • Seven Days |

    The week in science: Zoologists identify mislabelled carnivore as new species, leading forensic scientist resigns in China, and Ecuador opens way to drilling in Amazon reserve.


News Feature

  • News Feature |

    In a technical tour de force, Japanese researchers created eggs and sperm in the laboratory. Now, scientists have to determine how to use those cells safely — and ethically.

    • David Cyranoski


  • Comment |

    In decades of clinical-trial data, new treatments are better than standard ones just over half the time. That's as it should be, say Benjamin Djulbegovic and colleagues.

    • Benjamin Djulbegovic
    • Ambuj Kumar
    • Iain Chalmers

Books & Arts



News & Views

  • News & Views |

    Herbivory and mechanical wounding in plants have been shown to elicit electrical signals — mediated by two glutamate-receptor-like proteins — that induce defence responses at local and distant sites. See Article p.422

    • Alexander Christmann
    • Erwin Grill
  • News & Views |

    A correlation between stellar brightness variations and the gravitational acceleration at a star's surface has been observed that allows this acceleration to be measured with a precision of better than 25%. See Letter p.427

    • Jørgen Christensen-Dalsgaard
  • News & Views |

    The combination of two techniques — optogenetics and genome editing using engineered nucleases — now provides a general means for the light-controlled regulation of any gene of interest. See Letter p.472

    • Andreas Möglich
    • Peter Hegemann
  • News & Views |

    The observation of a triple point of coexistence between two insulating phases and a conducting phase in vanadium dioxide reveals physics that may help to unravel the role of electronic correlations in this material. See Letter p.431

    • Douglas Natelson
  • News & Views |

    The formation of new blood vessels from pre-existing ones is a carefully orchestrated dance. A study reveals that the metabolism of sugar by glycolysis contributes to its regulation.

    • Cholsoon Jang
    • Zoltan Arany
  • News & Views |

    How ecological network structures are influenced by species coexistence, community stability and perturbations is a topic of debate. It seems that one overlooked correlate of nested structures is species abundances. See Letter p.449

    • Colin Fontaine
  • News & Views |

    The far-reaching effects of the relationship between an animal and its resident gut microorganisms are becoming ever clearer. New findings suggest it can even create barriers that keep species separate.

    • Gregory D. D. Hurst
    • Chris D. Jiggins


  • Article |

    An analysis of mutations from over 7,000 cancers of diverse origins reveals the diversity of mutational processes underlying the development of cancer; more than 20 distinct mutational signatures are described, some of which are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are specific to individual tumour types.

    • Ludmil B. Alexandrov
    • Serena Nik-Zainal
    • Michael R. Stratton
  • Article |

    Upon wounding, plants mount a systemic response resulting in the production of jasmonates, hormones that confer resistance to herbivores; here we identify genes necessary for the electrical activity that leads to jasmonate synthesis far from the wound itself.

    • Seyed A. R. Mousavi
    • Adeline Chauvin
    • Edward E. Farmer


  • Letter |

    An analysis of archival data reveals an observational correlation between stellar brightness variations and surface gravity, allowing a determination of surface gravity with a precision of better than 25 per cent for inactive Sun-like stars at main-sequence to giant stages of evolution.

    • Fabienne A. Bastien
    • Keivan G. Stassun
    • Joshua Pepper
  • Letter |

    An annually resolved ice-core record from West Antarctica indicates that warming driven by local insolation resulting from sea-ice decline began in that region about 2,000 years before warming in East Antarctica, reconciling two alternative explanations for deglacial warming in the Southern Hemisphere.

    • T. J. Fudge
    • Eric J. Steig
    • Gifford J. Wong
  • Letter |

    Cooperation among species tends to result in mutualistic networks with a nested structure, which is thought to increase biodiversity and persistence but may be less stable than unstructured networks: here nested networks are shown to result from a mechanism that maximizes species abundances in mutualistic communities, and the abundance of nested species is found to be directly linked to the resilience of the community.

    • Samir Suweis
    • Filippo Simini
    • Amos Maritan
  • Letter | | Open Access

    The genome of the asexual rotifer Adineta vaga lacks homologous chromosomes; instead, its allelic regions are rearranged and sometimes found on the same chromosome in a palindromic fashion, a structure reminiscent of the primate Y chromosome and of other mitotic lineages such as cancer cells.

    • Jean-François Flot
    • Boris Hespeels
    • Karine Van Doninck
  • Letter |

    A human lipid transfer protein (GLTPD1, named here CPTP) is shown to regulate eicosanoid production by mediating the intermembrane transfer of the phosphorylated sphingolipid ceramide-1-phosphate through a non-vesicular transport mechanism elucidated by structural, functional and biological data.

    • Dhirendra K. Simanshu
    • Ravi Kanth Kamlekar
    • Dinshaw J. Patel
  • Letter |

    Here the customizable TALE DNA-binding domain was integrated with the light-sensitive cryptochrome 2 protein and its interacting partner (CIB1) from Arabidopsis thaliana, thereby creating an optogenetic two-hybrid system called light-inducible transcriptional effectors (LITEs); the LITE system establishes a novel mode of optogenetic control of endogenous transcription and epigenetic states.

    • Silvana Konermann
    • Mark D. Brigham
    • Feng Zhang
  • Letter |

    Whole-genome bisulphite sequencing data from diverse human cell and tissue types shows that only about 22% of CpGs change their methylation state across these cell types; most of these CpGs are located at gene regulatory elements, particularly enhancers and transcription-factor-binding sites, and these selected regions with dynamic DNA methylation patterns could help to define putative regulatory elements further.

    • Michael J. Ziller
    • Hongcang Gu
    • Alexander Meissner
  • Letter |

    The bacterial RecBCD helicase/nuclease shows broad, and apparently static, heterogeneity in the unwinding rate manifest by individual molecules: here it is shown that transiently halting an enzyme during processive translocation allows for a change, most likely conformational, such that the velocity of the molecule after pausing can fall anywhere within the spectrum of rates seen for a population.

    • Bian Liu
    • Ronald J. Baskin
    • Stephen C. Kowalczykowski
  • Letter |

    Folate receptor-α (FRα) is overexpressed in many cancer cells and is therefore an important therapeutic target: here the X-ray crystal structure of folate-bound FRα is presented, revealing details of the ligand-binding pocket that may be useful in the development of small-molecule inhibitors for anticancer therapy.

    • Chen Chen
    • Jiyuan Ke
    • Karsten Melcher







  • Futures |

    A universal feeling.

    • Marko Jankovic

Brief Communications Arising

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