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Volume 583 Issue 7818, 30 July 2020


This week marks the publication of results from phase three of the Encyclopedia of DNA Elements (ENCODE) project. Nine articles in this issue of Nature, along with papers published online and in several other journals, examine the most comprehensive catalogue yet of the candidate functional elements in the human and mouse genomes. In an overview paper, the ENCODE Project Consortium offers a summary of the new elements in the encyclopedia, which have been compiled with data sets from some 6,000 experiments. Much of the work published in this issue examines DNA regions called candidate cis-regulatory elements (cCREs), which may regulate gene transcription. Three papers — from Joseph Ecker, Bing Ren, Barbara Wold and their colleagues — look at cCREs during embryonic development in the mouse. Two papers from Wouter Meuleman, Jeff Vierstra, John Stamatoyannopoulos and colleagues map cCREs and transcription factor footprints in hundreds of human cell and tissue types. Michael Snyder and colleagues map chromatin loops in 24 human cell types; Eric Mendenhall and co-workers map the genome-wide binding of almost one-quarter of all chromatin-associated proteins active in a human liver cell line; and Brenton Graveley and colleagues integrate multiple assays to produce a comprehensive analysis of RNA-binding proteins and their functional elements. Finally, in a Perspective article, the project team puts the multiple phases of ENCODE in context.

Cover image: StoryTK

This Week

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News in Focus

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Books & Arts

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  • News & Views

    • A clinical trial has tested the use of gene-sequencing results for lung cancer to match patients to targeted therapies. Some paired treatments were a good fit, but others did not succeed, for reasons that will require further exploration.

      • Alexander Drilon
      • Matthew D. Hellmann
      News & Views
    • The prolonged cold of winter is required for the flowering of many plants. Now the identification of a previously unknown long-term cold-sensing mechanism helps to reveal how plants are able to time their flowering correctly.

      • Hiroyuki Iida
      • Ari Pekka Mähönen
      News & Views
  • Perspective

    • The authors summarize the history of the ENCODE Project, the achievements of ENCODE 1 and ENCODE 2, and how the new data generated and analysed in ENCODE 3 complement the previous phases.

      • Federico Abascal
      • Reyes Acosta
      • Richard M. Myers
  • Articles

    • ChIP–seq and CETCh–seq data are used to analyse binding maps for 208 transcription factors and other chromatin-associated proteins in a single human cell type, providing a comprehensive catalogue of the transcription factor landscape and gene regulatory networks in these cells.

      • E. Christopher Partridge
      • Surya B. Chhetri
      • Eric M. Mendenhall


      Article Open Access
    • A map of cohesin-mediated chromatin loops in 24 types of human cells identifies loops that show cell-type-specific variation, indicating that chromatin loops may help to specify cell-specific gene expression programs and functions.

      • Fabian Grubert
      • Rohith Srivas
      • Michael Snyder


      Article Open Access
    • The Phoenix stream in the Milky Way halo is shown to be a tidally disrupted remnant of an unusually metal-poor globular cluster, which was possibly destroyed during Galactic evolution.

      • Zhen Wan
      • Geraint F. Lewis
      • Gayandhi M. De Silva
    • A solution-based lithography-assisted epitaxial-growth-and-transfer method is used to fabricate single-crystal hybrid perovskites on any surface, with precise control of the thickness, area and chemical composition gradient.

      • Yusheng Lei
      • Yimu Chen
      • Sheng Xu
    • Current models are too noisy to predict climate usefully on decadal timescales, but two-stage post-processing of model outputs greatly improves predictions of decadal variations in North Atlantic winter climate.

      • D. M. Smith
      • A. A. Scaife
      • L. Zhang
    • Fishing has had a profound impact on global reef shark populations, and the absence or presence of sharks is strongly correlated with national socio-economic conditions and reef governance.

      • M. Aaron MacNeil
      • Demian D. Chapman
      • Joshua E. Cinner
    • Current outcomes are reported from the ongoing National Lung Matrix Trial, an umbrella trial for the treatment of non-small-cell lung cancer in which patients are triaged according to their tumour genotype and matched with targeted therapeutic agents.

      • Gary Middleton
      • Peter Fletcher
      • Lucinda Billingham

      Nature Outlook:

    • A study integrating single-cell RNA-sequencing and electrophysiology data shows that in mouse, the cellular repertoire of the thalamic reticular nucleus is characterized by a transcriptomic gradient defined at its extremes by mutually exclusive expression of Spp1 and Ecel1, providing insights into the organizational principles underlying the divergent functions of this brain region.

      • Yinqing Li
      • Violeta G. Lopez-Huerta
      • Guoping Feng
    • The authors find that slow plant growth at low temperatures during winter reduces dilution of the transcription factor NTL8, which allows slow accumulation of NTL8 and thus the gradual increase in transcription of VIN3—a gene involved in memory of cold exposure.

      • Yusheng Zhao
      • Rea L. Antoniou-Kourounioti
      • Martin Howard
    • Infection with SARS-CoV-2 causes interstitial pneumonia and viral replication in the lungs of transgenic mice that express a human version of ACE2, confirming the pathogenicity of the virus in this model.

      • Linlin Bao
      • Wei Deng
      • Chuan Qin
    • The pathogenicity and transmissibility of SARS-CoV-2 in golden (Syrian) hamsters resemble features of COVID-19 in human patients, suggesting that these hamsters could be used to model this disease.

      • Sin Fun Sia
      • Li-Meng Yan
      • Hui-Ling Yen
    • Analysis of B-cell leukaemia samples reveals that oncogenic mutations do not cause malignant transformation unless they converge on the same signalling pathway, and that it may be possible clinically to combine inhibition of the principal oncogenic driver with reactivation of divergent pathways.

      • Lai N. Chan
      • Mark A. Murakami
      • Markus Müschen
    • The histone variant H3.3 is phosphorylated at Ser31 in induced genes, and this selective mark stimulates the histone methyltransferase SETD2 and ejects the ZMYND11 repressor, thus revealing a role for histone phosphorylation in amplifying de novo transcription.

      • Anja Armache
      • Shuang Yang
      • Steven Z. Josefowicz
    • Single-molecule fluorescence resonance energy transfer and real-time confocal laser tracking with fluorescence correlation spectroscopy together characterize how individual lac repressor molecules bypass operator sites while exploring the DNA surface at microsecond timescales.

      • Emil Marklund
      • Brad van Oosten
      • Sebastian Deindl
    • A cryo-electron microscopy structure of the β1-adrenoceptor coupled to β-arrestin 1 and activated by the biased agonist formoterol, as well as the crystal structure of a related formoterol-bound adrenoreceptor, provide insights into biased signalling in these systems.

      • Yang Lee
      • Tony Warne
      • Christopher G. Tate
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Amendments & Corrections

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Nature Outlook

  • New therapies are turning cystic fibrosis, an inherited disorder that causes a vicious cycle of mucus build-up, infection and inflammation, into a more manageable condition that people can survive into adulthood.

    Nature Outlook
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