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  • Negative feedback buffers effects of regulatory variants
    1. Daniel M Bader1,
    2. Stefan Wilkening2,
    3. Gen Lin2,
    4. Manu M Tekkedil2,
    5. Kim Dietrich1,
    6. Lars M Steinmetz2,3,4 and
    7. Julien Gagneur*,1
    1. 1Computational Genomics, Gene Center, Ludwig Maximilians University, Munich, Germany
    2. 2European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany
    3. 3Stanford Genome Technology Center, Palo Alto, CA, USA
    4. 4Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA
    1. *Corresponding author. Tel: +49 89 218076742; E‐mail: gagneur{at}genzentrum.lmu.de

    Local trans regulation, mainly due to negative feedback, buffers effects of cis‐regulatory variants by about 15%. This buffering is stronger for essential genes and genes with low to middle expression levels, for which tight regulation matters most.

    Synopsis

    Local trans regulation, mainly due to negative feedback, buffers effects of cis‐regulatory variants by about 15%. This buffering is stronger for essential genes and genes with low to middle expression levels, for which tight regulation matters most.

    • Novel experimental design using expression of a diploid hybrid and its haploid spores allows systematic dissection of cis and local trans regulation.

    • Local trans effects buffer effects of cis‐regulatory variants in yeast by typically 15%.

    • Local trans buffering is primarily due to negative feedback.

    • Negative feedback as robustness strategy for genes with low to medium expression level.

    • buffering
    • canalization
    • cis regulation
    • feedback
    • trans regulation

    Mol Syst Biol. (2015) 11: 785

    • Received October 15, 2014.
    • Revision received December 19, 2014.
    • Accepted December 23, 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.

    Daniel M Bader, Stefan Wilkening, Gen Lin, Manu M Tekkedil, Kim Dietrich, Lars M Steinmetz, Julien Gagneur
  • From intracellular signaling to population oscillations: bridging size‐ and time‐scales in collective behavior
    1. Allyson E Sgro*,1,2,
    2. David J Schwab1,2,
    3. Javad Noorbakhsh3,
    4. Troy Mestler1,
    5. Pankaj Mehta3 and
    6. Thomas Gregor1,2
    1. 1Joseph Henry Laboratories of Physics, Princeton University, Princeton, NJ, USA
    2. 2Lewis‐Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA
    3. 3Department of Physics, Boston University, Boston, MA, USA
    1. *Corresponding author. Tel: +1 609 258 4335; E‐mail: asgro{at}princeton.edu

    A simple two‐variable model in combination with quantitative in vivo measurements of single‐cell and population signaling dynamics is used to analyze the emergence of collective cAMP oscillations in Dictyostelium discoideum.

    Synopsis

    A simple two‐variable model in combination with quantitative in vivo measurements of single‐cell and population signaling dynamics is used to analyze the emergence of collective cAMP oscillations in Dictyostelium discoideum.

    • Single Dictyostelium cells are well described as excitable, oscillatory systems.

    • A universal, top‐down model reproduces single‐cell and population‐level behaviors.

    • Model‐based predictions are validated in individual cells and in cellular populations.

    • Stochasticity drives the emergence and continued coordination of collective behavior.

    • dynamical systems
    • FRET
    • live microscopy
    • phenomenological modeling

    Mol Syst Biol. (2015) 11: 779

    • Received April 22, 2014.
    • Revision received December 13, 2014.
    • Accepted December 16, 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.

    Allyson E Sgro, David J Schwab, Javad Noorbakhsh, Troy Mestler, Pankaj Mehta, Thomas Gregor
  • Changing partners: transcription factors form different complexes on and off chromatin
    1. Zongling Ji1 and
    2. Andrew D Sharrocks (andrew.d.sharrocks{at}manchester.ac.uk) 1
    1. 1Faculty of Life Sciences, University of Manchester, Manchester, UK

    The current knowledge on how protein–protein interactions regulate the function of transcription factors (TFs) has remained limited due to an incomplete knowledge of their interaction partners. In their recent work, Chen and colleagues (Li et al, 2015) analyse the interactome of 56 TFs and reveal distinct chromatin‐associated and soluble TF complexes.

    See also: X Li et al (January 2015)

    A proteomic analysis of the interactomes of 56 transcription factors (TFs) by Chen and colleagues (Li et al, 2015) reveals distinct chromatin‐associated and soluble TF complexes and provides a resource for further analyses of TF function and regulation.

    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.

    Zongling Ji, Andrew D Sharrocks
  • Essential gene disruptions reveal complex relationships between phenotypic robustness, pleiotropy, and fitness
    1. Christopher R Bauer1,
    2. Shuang Li1 and
    3. Mark L Siegal*,1
    1. 1Department of Biology, NYU Center for Genomics and Systems Biology, New York, NY, USA
    1. *Corresponding author. Tel: +212 992 7908; E‐mail: mark.siegal{at}nyu.edu

    Mutations that alter expression of essential genes are potent regulators of phenotypic heterogeneity. Reducing gene function can result in global changes in morphological variation that are related to pleiotropy but initially have minimal impacts on fitness.

    Synopsis

    Mutations that alter expression of essential genes are potent regulators of phenotypic heterogeneity. Reducing gene function can result in global changes in morphological variation that are related to pleiotropy but initially have minimal impacts on fitness.

    • Proper expression of essential genes is critical for phenotypic robustness.

    • Release of phenotypic variation affects multiple independent phenotypes.

    • Mutations that reduce robustness also tend to be pleiotropic.

    • Reduction of phenotypic robustness generally precedes defects in fitness.

    • heterogeneity
    • pleiotropy
    • robustness
    • variation

    Mol Syst Biol. (2015) 11: 773

    • Received March 10, 2014.
    • Revision received November 17, 2014.
    • Accepted November 30, 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 R Bauer, Shuang Li, Mark L Siegal
  • Proteomic analyses reveal distinct chromatin‐associated and soluble transcription factor complexes
    1. Xu Li1,,
    2. Wenqi Wang1,,
    3. Jiadong Wang1,
    4. Anna Malovannaya2,
    5. Yuanxin Xi2,3,
    6. Wei Li2,3,
    7. Rudy Guerra4,
    8. David H Hawke5,
    9. Jun Qin2 and
    10. Junjie Chen*,1
    1. 1Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
    2. 2Department of Molecular and Cellular Biology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA
    3. 3Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA
    4. 4Department of Statistics, Rice University, Houston, TX, USA
    5. 5Proteomics Facility, Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
    1. *Corresponding author. Tel: +1 713 792 4863; Fax: +1 713 745 6141; E‐mail: jchen8{at}mdanderson.org
    1. These authors contributed equally to this work

    Chromatin‐associated and soluble complexes for 56 human transcription factors (TFs), identified by tandem affinity purification followed by mass spectrometry, indicate that distinct binding partners dictate the regulation and functions of TFs.

    Synopsis

    Chromatin‐associated and soluble complexes for 56 human transcription factors (TFs), identified by tandem affinity purification followed by mass spectrometry, indicate that distinct binding partners dictate the regulation and functions of TFs.

    • 2,156 high‐confident interactions are identified by TAP/MS for 56 human TFs, including 37 members of the Forkhead box (FOX) TF family.

    • TFs form distinct complexes on and off chromatin.

    • Different TF‐binding partners dictate the specific regulation and diverse functions of these TFs.

    • forkhead box
    • mass spectrometry
    • protein–protein interaction
    • transcriptional factor

    Mol Syst Biol. (2015) 11: 775

    • Received June 18, 2014.
    • Revision received November 25, 2014.
    • Accepted December 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.

    Xu Li, Wenqi Wang, Jiadong Wang, Anna Malovannaya, Yuanxin Xi, Wei Li, Rudy Guerra, David H Hawke, Jun Qin, Junjie Chen
  • Defining a minimal cell: essentiality of small ORFs and ncRNAs in a genome‐reduced bacterium
    1. Maria Lluch‐Senar*,1,2,,
    2. Javier Delgado1,2,,
    3. Wei‐Hua Chen3,,
    4. Verónica Lloréns‐Rico1,2,
    5. Francis J O'Reilly3,
    6. Judith AH Wodke1,2,4,
    7. E Besray Unal1,2,
    8. Eva Yus1,2,
    9. Sira Martínez1,2,
    10. Robert J Nichols5,
    11. Tony Ferrar1,2,
    12. Ana Vivancos6,
    13. Arne Schmeisky7,
    14. Jörg Stülke7,
    15. Vera van Noort8,
    16. Anne‐Claude Gavin3,
    17. Peer Bork3,9 and
    18. Luis Serrano*,1,2,10
    1. 1EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Barcelona, Spain
    2. 2Universitat Pompeu Fabra (UPF), Barcelona, Spain
    3. 3European Molecular Biology Laboratory, Heidelberg, Germany
    4. 4Theoretical Biophysics, Humboldt‐Universität zu Berlin, Berlin, Germany
    5. 5Department of Genetics, Stanford University, Stanford, CA, USA
    6. 6Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
    7. 7Department of General Microbiology, Institute for Microbiology and Genetics, Göttingen, Germany
    8. 8Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium
    9. 9Max‐Delbrück‐Centre (MDC) for Molecular Medicine, Berlin, Germany
    10. 10Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
    1. * Corresponding author. Tel: +34 933160186; E‐mail: maria.lluch{at}crg.es

      Corresponding author. Tel: +34 933160101; E‐mail: luis.serrano{at}crg.es

    1. These authors contributed equally to this work

    A genome essentiality analysis in the genome‐reduced bacterium Mycoplasma pneumoniae, reveals that protein essentiality should be considered at the domain level and that small proteins (< 100 aa) and ncRNAs are frequently essential genomic elements.

    Synopsis

    A genome essentiality analysis in the genome‐reduced bacterium Mycoplasma pneumoniae, reveals that protein essentiality should be considered at the domain level and that small proteins (< 100 aa) and ncRNAs are frequently essential genomic elements.

    • A genome essentiality analysis is performed using two mini‐transposon mutant libraries of M. pneumoniae.

    • The results indicate that ORF essentiality should be considered at the protein domain level.

    • Small ORFs are as essential as conventional ORFs and they can interact with DNA.

    • Some essential antisense ncRNAs are involved in the regulation of essential ORF expression.

    • minimal genome
    • non‐coding RNAs
    • small proteins

    Mol Syst Biol. (2015) 11: 780

    • Received July 7, 2014.
    • Revision received December 15, 2014.
    • Accepted December 18, 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.

    Maria Lluch‐Senar, Javier Delgado, Wei‐Hua Chen, Verónica Lloréns‐Rico, Francis J O'Reilly, Judith AH Wodke, E Besray Unal, Eva Yus, Sira Martínez, Robert J Nichols, Tony Ferrar, Ana Vivancos, Arne Schmeisky, Jörg Stülke, Vera van Noort, Anne‐Claude Gavin, Peer Bork, Luis Serrano
  • Linked circadian outputs control elongation growth and flowering in response to photoperiod and temperature
    1. Daniel D Seaton1,,
    2. Robert W Smith14,
    3. Young Hun Song25,
    4. Dana R MacGregor36,
    5. Kelly Stewart1,
    6. Gavin Steel1,
    7. Julia Foreman1,
    8. Steven Penfield36,
    9. Takato Imaizumi2,
    10. Andrew J Millar1 and
    11. Karen J Halliday*,1
    1. 1SynthSys and School of Biological Sciences, University of Edinburgh, Edinburgh, UK
    2. 2Department of Biology, University of Washington, Seattle, WA, USA
    3. 3Biosciences, University of Exeter, Exeter, UK
    4. 4Laboratory of Systems & Synthetic Biology, Wageningen UR, Wageningen, The Netherlands
    5. 5Department of Life Sciences, Ajou University, Suwon, South Korea
    6. 6Department of Crop Genetics, John Innes Centre, Norwich, UK
    1. *Corresponding author. Tel: +44 131 651 9083; E‐mail: karen.halliday{at}ed.ac.uk

    Crosstalk between the circadian clock and light/temperature signals controls seasonal plant development. Integrated mathematical models of the clock, flowering and elongation pathways identify new behaviours in light and temperature signalling.

    Synopsis

    Crosstalk between the circadian clock and light/temperature signals controls seasonal plant development. Integrated mathematical models of the clock, flowering and elongation pathways identify new behaviours in light and temperature signalling.

    • CCA1 negatively regulates FKF1 and CDF1 transcription.

    • GI has an FKF1‐independent role in CDF1 protein stabilisation.

    • PIF proteins function throughout light:dark cycles.

    • Temperature regulates flowering time and hypocotyl elongation pathways at distinct times of day.

    • gene regulatory networks
    • heat
    • hypocotyl elongation
    • photoperiodism
    • seasonal breeding

    Mol Syst Biol. (2015) 11: 776

    • Received September 15, 2014.
    • Revision received November 21, 2014.
    • Accepted December 5, 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.

    Daniel D Seaton, Robert W Smith, Young Hun Song, Dana R MacGregor, Kelly Stewart, Gavin Steel, Julia Foreman, Steven Penfield, Takato Imaizumi, Andrew J Millar, Karen J Halliday