Advertisement

  • Phosphorylation of ubiquitin at Ser65 affects its polymerization, targets, and proteome‐wide turnover
    Phosphorylation of ubiquitin at Ser65 affects its polymerization, targets, and proteome‐wide turnover
    1. Danielle L Swaney1,,
    2. Ricard A Rodríguez‐Mias1, and
    3. Judit Villén*,1
    1. 1Department of Genome Sciences, University of Washington, Seattle, WA, USA
    1. *Corresponding author. Tel: +1 206 685 1490; E‐mail: jvillen{at}u.washington.edu
    1. These authors contributed equally to this work

    This study explores the functional consequences of ubiquitin phosphorylation at Ser65. This modification is found to be induced by oxidative stress and have profound effects on ubiquitin chain disassembly, linkage, and substrate targeting.

    Synopsis

    This study explores the functional consequences of ubiquitin phosphorylation at Ser65. This modification is found to be induced by oxidative stress and have profound effects on ubiquitin chain disassembly, linkage, and substrate targeting.

    • The impact of ubiquitin S65 phosphorylation is assessed in Saccharomyces cerevisiae.

    • Quantitative proteomics shows that oxidative stress leads to up‐regulation of ubiquitin S65 phosphorylation and the accumulation of several types of ubiquitin chains.

    • The effects of S65 phosphomimetic mutation on ubiquitin biochemistry are widespread: chain assembly, disassembly, chain linkage distribution, and protein–protein interactions.

    • Ubiquitin S65 phosphomimetic mutation leads to the accumulation of polyubiquitinated species and affects substrate half‐lives in vivo.

    • oxidative stress
    • phosphorylation
    • protein turnover
    • proteomics
    • ubiquitin
    • Received February 27, 2015.
    • Revision received June 15, 2015.
    • Accepted June 15, 2015.
    Danielle L Swaney, Ricard A Rodríguez‐Mias, Judit Villén
  • Venus trap in the mouse embryo reveals distinct molecular dynamics underlying specification of first embryonic lineages
    Venus trap in the mouse embryo reveals distinct molecular dynamics underlying specification of first embryonic lineages
    1. Jens‐Erik Dietrich15,
    2. Laura Panavaite1,,
    3. Stefan Gunther2,
    4. Sebastian Wennekamp1,
    5. Anna C Groner36,
    6. Anton Pigge4,
    7. Stefanie Salvenmoser1,
    8. Didier Trono3,
    9. Lars Hufnagel2 and
    10. Takashi Hiiragi*,1
    1. 1Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
    2. 2Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
    3. 3School of Life Sciences Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
    4. 4Max Planck Institute for Molecular Biomedicine, Muenster, Germany
    5. 5Department of Gynecologic Endocrinology and Fertility Disorders, Heidelberg University Women's Hospital, Heidelberg, Germany
    6. 6 Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana‐Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
    1. *Corresponding author. Tel: +49 6221 3878844; E‐mail: hiiragi{at}embl.de
    1. These authors contributed equally to this work

    Systematic analyses of a comprehensive map of mouse pre‐implantation development reveal that the timing and mechanism of lineage specification may be different between the trophectoderm and the inner cell mass.

    Synopsis

    Systematic analyses of a comprehensive map of mouse pre‐implantation development reveal that the timing and mechanism of lineage specification may be different between the trophectoderm and the inner cell mass.

    • Venus‐trap screen in the mouse blastocyst generates fluorescent lineage reporter mice.

    • A comprehensive lineage map of mouse pre‐implantation development integrates lineage track, cell position and gene expression dynamics.

    • Systematic analyses of the map represent a framework toward systems‐level understanding of embryogenesis marked by high dynamicity and variability.

    • gene trap
    • lineage map
    • live imaging
    • mouse
    • pre‐implantation development
    • Received January 27, 2015.
    • Revision received June 2, 2015.
    • Accepted June 2, 2015.
    Jens‐Erik Dietrich, Laura Panavaite, Stefan Gunther, Sebastian Wennekamp, Anna C Groner, Anton Pigge, Stefanie Salvenmoser, Didier Trono, Lars Hufnagel, Takashi Hiiragi
  • Removal of H2A.Z by INO80 promotes homologous recombination
    Removal of H2A.Z by INO80 promotes homologous recombination
    1. Hanan E Alatwi1 and
    2. Jessica A Downs*,1
    1. 1MRC Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, UK
    1. *Corresponding author. Tel: +44 1273 678 369; E‐mail: j.a.downs{at}sussex.ac.uk

    This study shows that a major function of the human INO80 chromatin‐remodeling complex in homologous recombination is the removal of H2A.Z from damaged chromatin.

    Synopsis

    This study shows that a major function of the human INO80 chromatin‐remodeling complex in homologous recombination is the removal of H2A.Z from damaged chromatin.

    • H2A.Z is rapidly incorporated and then removed from chromatin flanking DNA damage.

    • Removal of H2A.Z from damaged chromatin depends on INO80.

    • Loss of either INO80 or the histone chaperone ANP32E, which also promotes H2A.Z removal, leads to a defect in RAD51 foci formation after damage.

    • Repair defects in cells depleted of INO80 or ANP32E can be rescued by H2A.Z co‐depletion.

    • ANP32E
    • chromatin
    • H2A.Z
    • homologous recombination
    • INO80
    • Received March 5, 2015.
    • Revision received June 9, 2015.
    • Accepted June 10, 2015.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Hanan E Alatwi, Jessica A Downs
  • Host ER stress during malaria parasite infection
    Host ER stress during malaria parasite infection
    1. Alexis Kaushansky1 and
    2. Stefan HI Kappe (stefan.kappe{at}cidresearch.org)1,2
    1. 1Center for Infectious Disease Research, Formerly Seattle Biomedical Research Institute, Seattle, WA, USA
    2. 2Department of Global Health, University of Washington, Seattle, WA, USA

    After transmission by Anopheles mosquitoes, malaria parasite sporozoites target the liver, where they infect hepatocytes and multiply thousands of times. The release of new parasites into the blood stream then initiates symptomatic red blood cell infection. Although successful replication within hepatocytes is critical for host infection, little is known about parasite–hepatocyte interactions that ensure parasite survival and development. In this issue of EMBO Reports, the Mota group describes a beneficial role of the host ER stress pathway for Plasmodium survival in infected hepatocytes [1]. They demonstrate that proteins and transcripts that act in the unfolded protein response (UPR) are elevated in hepatocytes in response to infection. Reversing these perturbations by eliminating the splicing of XBP1 or knockdown of CREBH is detrimental to parasite development. These findings are of significant interest in light of recent findings that elucidate other aspects of liver‐stage parasite–hepatocyte interactions and raise new, intriguing questions for the field (Fig 1).

    See also: P Inácio et al

    Infection of hepatocytes by the malaria parasite is shown in this issue of EMBO Reports to trigger the host ER stress response, which benefits parasite survival and growth. This pathway could thus become a target for therapeutic intervention.

    Alexis Kaushansky, Stefan HI Kappe
  • Ethics and germline gene editing
    Ethics and germline gene editing
    1. Jeremy Sugarman (jsugarman{at}jhu.edu)1
    1. 1Johns Hopkins Berman Institute of Bioethics, Baltimore, MD, USA

    Instead of calling for a moratorium or discussion on the specific use of CRISPR/Cas9 to edit the human germline, we should develop global guidelines for all new assisted reproductive technologies as they are developed.

    Jeremy Sugarman
  • Brahma is required for cell cycle arrest and late muscle gene expression during skeletal myogenesis
    Brahma is required for cell cycle arrest and late muscle gene expression during skeletal myogenesis
    1. Sonia Albini1,,
    2. Paula Coutinho Toto1,,
    3. Alessandra Dall'Agnese1,
    4. Barbora Malecova1,
    5. Carlo Cenciarelli2,
    6. Armando Felsani3,
    7. Maurizia Caruso3,
    8. Scott J Bultman4 and
    9. Pier Lorenzo Puri*,1,5
    1. 1Sanford‐Burnham Institute for Medical Research, La Jolla, CA, USA
    2. 2CNR‐Istituto di Farmacologia Traslazionale, Rome, Italy
    3. 3CNR‐Istituto di Biologia Cellulare e Neurobiologia Fondazione Santa Lucia, Rome, Italy
    4. 4Department of Genetics, Lineberger Comprehensive Cancer Center University of North Carolina, Chapel Hill, NC, USA
    5. 5IRCCS Fondazione Santa Lucia, Rome, Italy
    1. *Corresponding author. Tel: +1 858 646 3161; E‐mail: lpuri{at}sanfordburnham.org
    1. These authors contributed equally to this work

    The two catalytic subunits of the SWI/SNF chromatin‐remodeling complex have distinct functions during skeletal muscle differentiation. Brm promotes cell cycle arrest by repressing cyclin D1, controls satellite cell proliferation and activates late muscle genes, while Brg1 activates muscle genes at early stages of myogenesis.

    Synopsis

    The two catalytic subunits of the SWI/SNF chromatin‐remodeling complex have distinct functions during skeletal muscle differentiation. Brm promotes cell cycle arrest by repressing cyclin D1, controls satellite cell proliferation and activates late muscle genes, while Brg1 activates muscle genes at early stages of myogenesis.

    • Brm and Brg1 regulate distinct stages of muscle differentiation during skeletal myogenesis.

    • Brm‐mediated repression of cyclin D1 is required for myoblast cell cycle arrest prior to differentiation.

    • Brm is required for activation of late muscle differentiation and proper muscle regeneration.

    • Brahma
    • cyclin D1
    • skeletal myogenesis
    • SNF/SWI
    • transcription
    • Received January 27, 2015.
    • Revision received May 21, 2015.
    • Accepted May 25, 2015.
    Sonia Albini, Paula Coutinho Toto, Alessandra Dall'Agnese, Barbora Malecova, Carlo Cenciarelli, Armando Felsani, Maurizia Caruso, Scott J Bultman, Pier Lorenzo Puri
  • The RNA surveillance complex Pelo‐Hbs1 is required for transposon silencing in the Drosophila germline
    <div xmlns="http://www.w3.org/1999/xhtml">The RNA surveillance complex Pelo‐Hbs1 is required for transposon silencing in the <em>Drosophila</em> germline</div>
    1. Fu Yang1,2,
    2. Rui Zhao2,
    3. Xiaofeng Fang3,4,
    4. Huanwei Huang2,
    5. Yang Xuan2,
    6. Yanting Ma2,
    7. Hongyan Chen2,
    8. Tao Cai2,
    9. Yijun Qi3,4 and
    10. Rongwen Xi*,2
    1. 1College of Life Sciences Beijing Normal University, Beijing, China
    2. 2National Institute of Biological Sciences, Beijing, China
    3. 3Tsinghua‐Peking Center for Life Sciences, Beijing, China
    4. 4Center for Plant Biology, School of Life Sciences Tsinghua University, Beijing, China
    1. *Corresponding author. Tel: +86 10 80723241; Fax: +86 10 80723249; E‐mail: xirongwen{at}nibs.ac.cn

    The Pelo (Dom34)‐Hbs1 mRNA surveillance complex is required for transposon silencing in the Drosophila germline, which reveals a novel mechanism of transposon silencing possibly at the translational level.

    Synopsis

    The Pelo (Dom34)‐Hbs1 mRNA surveillance complex is required for transposon silencing in the Drosophila germline, which reveals a novel mechanism of transposon silencing possibly at the translational level.

    • Loss of Pelo causes up‐regulation of specific transposable elements (TEs) in both ovaries and testes.

    • Pelo is not required in the piRNA pathway.

    • Pelo functionally interacts with Hbs1 in TE silencing, and RpS30a overexpression partially rescues TE silencing defects in pelo mutants.

    • Drosophila
    • germline
    • Hbs1
    • Pelota/Dom34
    • transposon silencing
    • Received January 13, 2015.
    • Revision received May 27, 2015.
    • Accepted June 2, 2015.
    Fu Yang, Rui Zhao, Xiaofeng Fang, Huanwei Huang, Yang Xuan, Yanting Ma, Hongyan Chen, Tao Cai, Yijun Qi, Rongwen Xi