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  • An organ boundary‐enriched gene regulatory network uncovers regulatory hierarchies underlying axillary meristem initiation
    1. Caihuan Tian1,
    2. Xiaoni Zhang1,2,
    3. Jun He1,
    4. Haopeng Yu1,3,
    5. Ying Wang1,
    6. Bihai Shi1,3,
    7. Yingying Han1,3,
    8. Guoxun Wang1,3,
    9. Xiaoming Feng1,
    10. Cui Zhang1,
    11. Jin Wang1,3,
    12. Jiyan Qi1,3,
    13. Rong Yu2 and
    14. Yuling Jiao*,1
    1. 1State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and National Center for Plant Gene Research, Beijing, China
    2. 2College of Life Sciences, Capital Normal University, Beijing, China
    3. 3University of Chinese Academy of Sciences, Beijing, China
    1. *Corresponding author. Tel: +86 10 64807656; Fax: +86 10 64806595; E‐mail: yljiao{at}genetics.ac.cn

    The leaf boundary regions separate differentiated organs from undifferentiated stem cells in plants. The gene regulatory network of boundary cells was mapped by combining cell type‐specific genome expression analysis with genomewide yeast one‐hybrid screening.

    Synopsis

    The leaf boundary regions separate differentiated organs from undifferentiated stem cells in plants. The gene regulatory network of boundary cells was mapped by combining cell type‐specific genome expression analysis with genomewide yeast one‐hybrid screening.

    • A leaf boundary cell‐specific gene expression map identifies transcriptional signatures and predicts cellular functions.

    • A genomewide protein–DNA interaction map resolved using a yeast one‐hybrid approach uncovers promoter hubs and predicts new regulating transcription factors (TFs).

    • An intermediate‐scale experimental test determined the regulatory effects of many TFs on their targets and identified new regulators and regulatory relationships in boundary and axillary meristem formation.

    • axillary meristem
    • gene regulatory network
    • organ boundary

    Mol Syst Biol. (2014) 10: 755

    • Received June 3, 2014.
    • Revision received August 14, 2014.
    • Accepted September 24, 2014.

    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.

    Caihuan Tian, Xiaoni Zhang, Jun He, Haopeng Yu, Ying Wang, Bihai Shi, Yingying Han, Guoxun Wang, Xiaoming Feng, Cui Zhang, Jin Wang, Jiyan Qi, Rong Yu, Yuling Jiao
  • Ultrasensitive proteome analysis using paramagnetic bead technology
    1. Christopher S Hughes1,
    2. Sophia Foehr1,
    3. David A Garfield1,
    4. Eileen E Furlong1,
    5. Lars M Steinmetz1 and
    6. Jeroen Krijgsveld*,1
    1. 1European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany
    1. *Corresponding author. Tel: +49 6221 3878560; E‐mail: jeroen.krijgsveld{at}embl.de

    A new proteomic sample preparation protocol allows fast, efficient and ultra‐sensitive analyses. The method is illustrated by profiling proteomes from sub‐microgram amounts of material, including the first proteome screen of Drosophila development at a single‐embryo resolution.

    Synopsis

    A new proteomic sample preparation protocol allows fast, efficient and ultra‐sensitive analyses. The method is illustrated by profiling proteomes from sub‐microgram amounts of material, including the first proteome screen of Drosophila development at a single‐embryo resolution.

    • A novel protocol using paramagnetic beads, termed Single‐Pot Solid‐Phase‐enhanced Sample Preparation (SP3) is presented.

    • SP3 enables protein and peptide enrichment, cleanup, digestion, chemical isotope labeling and fractionation in a single tube, without limitations arising from reagent compatibility.

    • SP3 allows unmatched ultra‐sensitive proteome profiling from sub‐microgram amounts of material, as low as 1,000 HeLa cells or a single fly embryo.

    • The first quantitative analysis of early Drosophila development at a single‐embryo resolution reveals dynamic trends in the developmental proteome.

    • mass spectrometry
    • paramagnetic beads
    • proteomics
    • quantification
    • sample preparation

    Mol Syst Biol. (2014) 10: 757

    • Received July 27, 2014.
    • Revision received October 1, 2014.
    • Accepted October 7, 2014.

    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.

    Christopher S Hughes, Sophia Foehr, David A Garfield, Eileen E Furlong, Lars M Steinmetz, Jeroen Krijgsveld
  • Efficient sample processing for proteomics applications—Are we there yet?
    1. Evgeny Kanshin1 and
    2. Pierre Thibault (pierre.thibault{at}umontreal.ca) 1,2
    1. 1Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada
    2. 2Department of Chemistry, Université de Montréal, Montréal, QC, Canada

    The ability to solubilize and digest protein extracts and recover peptides with high efficiency is of paramount importance in proteomics. A novel proteomic sample preparation protocol by Krijgsveld and colleagues (Hughes et al, 2014) provides significant advantages by enabling all sample processing steps to be carried out in a single tube to minimize sample losses, thereby enhancing sensitivity, throughput, and scalability of proteomics analyses.

    See also: Hughes et al (October 2014)

    A new proteomic sample preparation protocol by Krijgsveld and colleagues (Hughes et al, 2014) enables all sample processing steps to be carried out in a single tube to minimize sample losses, thereby enhancing sensitivity, throughput, and scalability of proteomics analyses.

    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.

    Evgeny Kanshin, Pierre Thibault
  • Constant rate of p53 tetramerization in response to DNA damage controls the p53 response
    1. Giorgio Gaglia1 and
    2. Galit Lahav*,1
    1. 1Department of Systems Biology, Harvard Medical School, Boston, MA, USA
    1. *Corresponding author. Tel: +1 617 432 5621; Fax: +1 617 432 5012; E‐mail: galit{at}hms.harvard.edu

    Quantification of the dynamics of p53 tetramers in single cells using a fluorescent protein‐fragment complementation assay reveals that, while total p53 increases proportionally to the DNA damage strength, p53 tetramers are formed at a constant rate.

    Synopsis

    Quantification of the dynamics of p53 tetramers in single cells using a fluorescent protein‐fragment complementation assay reveals that, while total p53 increases proportionally to the DNA damage strength, p53 tetramers are formed at a constant rate.

    • A fluorescent protein‐fragment complementation assay is developed and used to quantify p53 tetramers in single living cells.

    • In response to DNA damage, p53 total levels increase proportionally to the strength of the damage; however, p53 tetramers are formed at a constant rate across damage doses.

    • The protein ARC is a key component of the “molecular throttle” that controls the rate of p53 tetramer formation and breaks the linear relationship between the input strength (DNA damage) and cellular output (active p53).

    • In the absence of ARC, the rate of p53 tetramerization becomes dose dependent and the expression of p53 target genes is enhanced.

    • DNA damage
    • fluorescence imaging
    • p53 dynamics
    • single cells
    • tetramers

    Mol Syst Biol. (2014) 10: 753

    • Received January 13, 2014.
    • Revision received September 4, 2014.
    • Accepted September 8, 2014.

    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.

    Giorgio Gaglia, Galit Lahav
  • Allelic expression mapping across cellular lineages to establish impact of non‐coding SNPs
    1. Veronique Adoue1,
    2. Alicia Schiavi2,,
    3. Nicholas Light2,,
    4. Jonas Carlsson Almlöf3,
    5. Per Lundmark3,
    6. Bing Ge2,
    7. Tony Kwan2,
    8. Maxime Caron2,
    9. Lars Rönnblom4,
    10. Chuan Wang3,
    11. Shu‐Huang Chen2,
    12. Alison H Goodall5,6,7,
    13. Francois Cambien7,8,
    14. Panos Deloukas7,9,
    15. Willem H Ouwehand7,10,11,
    16. Ann‐Christine Syvänen3 and
    17. Tomi Pastinen*,2
    1. 1Institute National de la Santé et de la Recherche Médicale (INSERM), U1043, Toulouse, France
    2. 2Department of Human Genetics, McGill University and Genome Quebec Innovation Centre, Montreal, QC, Canada
    3. 3Department of Medical Sciences, Molecular Medicine, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
    4. 4Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
    5. 5Department of Cardiovascular Science, University of Leicester, Leicester, UK
    6. 6Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, UK
    7. 7Cardiogenics Consortium
    8. 8INSERM UMRS 937 Pierre and Marie Curie University and Medical School, Paris, France
    9. 9Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
    10. 10Department of Haematology, University of Cambridge, Cambridge, UK
    11. 11National Health Service Blood and Transplant, Cambridge Centre, Cambridge, UK
    1. *Corresponding author. Tel: +1 514 398 1777; E‐mail: tomi.pastinen{at}mcgill.ca
    1. These authors contributed equally to this work

    A comprehensive analysis cis‐variation in four cell‐populations uncovers a new‐class of cis‐regulatory SNPs associated with repressor activity. Global analysis of the role of key regulators is achieved by combining allelic expression read‐outs with targeted perturbation of transcription factors.

    Synopsis

    A comprehensive analysis cis‐variation in four cell‐populations uncovers a new‐class of cis‐regulatory SNPs associated with repressor activity. Global analysis of the role of key regulators is achieved by combining allelic expression read‐outs with targeted perturbation of transcription factors.

    • Direct mapping of cis‐regulatory SNPs in human tissues and populations reveals that greater than 50% of effects are shared and 5–10% of variants impact expression in regional rather than transcript‐specific manner.

    • A new class of cis‐rSNPs is uncovered, which disrupts footprint‐derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs.

    • A new approach is presented for the genome‐wide functional validation of transcription factor – SNP interactions using small molecule perturbation and allelic expression monitoring.

    • allelic expression
    • cis‐rSNPs
    • complex disease
    • NFκB
    • repressor

    Mol Syst Biol. (2014) 10: 754

    • Received January 13, 2014.
    • Revision received September 9, 2014.
    • Accepted September 11, 2014.

    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.

    Veronique Adoue, Alicia Schiavi, Nicholas Light, Jonas Carlsson Almlöf, Per Lundmark, Bing Ge, Tony Kwan, Maxime Caron, Lars Rönnblom, Chuan Wang, Shu‐Huang Chen, Alison H Goodall, Francois Cambien, Panos Deloukas, Willem H Ouwehand, Ann‐Christine Syvänen, Tomi Pastinen
  • Plasma membrane H+‐ATPase regulation is required for auxin gradient formation preceding phototropic growth
    1. Tim Hohm1,2,,
    2. Emilie Demarsy3,,
    3. Clément Quan3,
    4. Laure Allenbach Petrolati3,
    5. Tobias Preuten3,
    6. Teva Vernoux4,
    7. Sven Bergmann*,1,2, and
    8. Christian Fankhauser*,3,
    1. 1Department of Medical Genetics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
    2. 2Swiss Institute for Bioinformatics, Lausanne, Switzerland
    3. 3Centre for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
    4. 4Laboratoire de Reproduction et Développement des Plantes, CNRS INRA ENS Lyon UCBL Université de Lyon, Lyon, France
    1. * Corresponding author. Tel: +41 21 692 5452; E‐mail: sven.bergmann{at}unil.ch

      Corresponding author. Tel: +41 21 692 3941; E‐mail: christian.fankhauser{at}unil.ch

    1. These authors contributed equally to this work

    2. These authors contributed equally to this work

    In silico and in planta analyses of the contribution of morphological and biophysical parameters to auxin relocalization in phototropism reveal the importance of light‐dependent regulation of apoplastic pH and of cellular topology.

    Synopsis

    In silico and in planta analyses of the contribution of morphological and biophysical parameters to auxin relocalization in phototropism reveal the importance of light‐dependent regulation of apoplastic pH and of cellular topology.

    • Regulation of apoplastic pH is a key feature for the establishment of a lateral auxin gradient leading to phototropism.

    • The phototropin photoreceptors regulate the activity of plasma membrane‐associated H+‐ATPase which are major regulators of apoplastic pH.

    • Cellular topology has a strong impact on lateral auxin gradient formation.

    • auxin
    • modeling
    • phototropins
    • phototropism
    • plasma membrane H+‐ATPase

    Mol Syst Biol. (2014) 10: 751

    • Received March 2, 2014.
    • Revision received August 20, 2014.
    • Accepted August 22, 2014.

    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.

    Tim Hohm, Emilie Demarsy, Clément Quan, Laure Allenbach Petrolati, Tobias Preuten, Teva Vernoux, Sven Bergmann, Christian Fankhauser
  • The role of the interactome in the maintenance of deleterious variability in human populations
    1. Luz Garcia‐Alonso1,
    2. Jorge Jiménez‐Almazán1,2,
    3. Jose Carbonell‐Caballero1,
    4. Alicia Vela‐Boza3,
    5. Javier Santoyo‐López3,
    6. Guillermo Antiñolo3,4,5 and
    7. Joaquin Dopazo*,1,2,3,6
    1. 1Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain
    2. 2Bioinformatics of Rare Diseases (BIER), CIBER de Enfermedades Raras (CIBERER), Valencia, Spain
    3. 3Medical Genome Project, Genomics and Bioinformatics Platform of Andalusia (GBPA), Seville, Spain
    4. 4Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville, University Hospital Virgen del Rocio/Consejo Superior de Investigaciones Científicas/University of Seville, Seville, Spain
    5. 5Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Seville, Spain
    6. 6Functional Genomics Node, (INB) at CIPF, Valencia, Spain
    1. *Corresponding author. Tel: +34 96 328 9680; E‐mail: jdopazo{at}cipf.es

    Analysis of genetic variability in 1,330 personal genomes obtained by exome sequencing of healthy individuals indicates that deleterious mutations preferentially accumulate in the periphery of the interactome and occur in specific combinations that minimally disrupt its structure.

    Synopsis

    Analysis of genetic variability in 1,330 personal genomes obtained by exome sequencing of healthy individuals indicates that deleterious mutations preferentially accumulate in the periphery of the interactome and occur in specific combinations that minimally disrupt its structure.

    • The large mutational load of human genome was analyzed in the context of the protein interactome.

    • Deleterious mutations tolerated by healthy individuals are found to accumulate in the periphery of the interactome.

    • Such mutations only occur in specific epistatic combinations that minimize the impact over the interactome.

    • The study suggests that the pathological potential of a variant seems to be more a systems property than an intrinsic property of individual proteins.

    • exome sequencing
    • interactome
    • mutational load
    • network analysis
    • robustness

    Mol Syst Biol. (2014) 10: 752

    • Received February 22, 2014.
    • Revision received August 23, 2014.
    • Accepted August 28, 2014.

    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.

    Luz Garcia‐Alonso, Jorge Jiménez‐Almazán, Jose Carbonell‐Caballero, Alicia Vela‐Boza, Javier Santoyo‐López, Guillermo Antiñolo, Joaquin Dopazo

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