Large-Scale Public Transcriptomic Data Mining Reveals a Tight Connection between the Transport of Nitrogen and Other Transport Processes in Arabidopsis

Movement of nitrogen to the plant tissues where it is needed for growth is an important contribution to nitrogen use efficiency. However, we have very limited knowledge about the mechanisms of nitrogen transport. Loading of nitrogen into the xylem and/or phloem by transporter proteins is likely important, but there are several families of genes that encode transporters of nitrogenous molecules (collectively referred to as N transporters here), each comprised of many gene members. In this study, we leveraged publicly available microarray data of Arabidopsis to investigate the gene networks of N transporters to elucidate their possible biological roles. First, we showed that tissue-specificity of nitrogen (N) transporters was well reflected among the public microarray data. Then, we built coexpression networks of N transporters, which showed relationships between N transporters and particular aspects of plant metabolism, such as phenylpropanoid biosynthesis and carbohydrate metabolism. Furthermore, genes associated with several biological pathways were found to be tightly coexpressed with N transporters in different tissues. Our coexpression networks provide information at the systems-level that will serve as a resource for future investigation of nitrogen transport systems in plants, including candidate gene clusters that may work together in related biological roles.

[1]  Simon Newstead,et al.  Molecular basis of nitrate uptake by the plant nitrate transporter NRT1.1 , 2014, Nature.

[2]  John Ralph,et al.  Caffeoyl Shikimate Esterase (CSE) Is an Enzyme in the Lignin Biosynthetic Pathway in Arabidopsis , 2013, Science.

[3]  Angela Hodge,et al.  The plastic plant: root responses to heterogeneous supplies of nutrients , 2004 .

[4]  Staffan Persson,et al.  Co-expression tools for plant biology: opportunities for hypothesis generation and caveats. , 2009, Plant, cell & environment.

[5]  H. Nam,et al.  Leaf senescence. , 2007, Annual review of plant biology.

[6]  S. Drăghici,et al.  Analysis of microarray experiments of gene expression profiling. , 2006, American journal of obstetrics and gynecology.

[7]  Tong Zhu,et al.  Global transcription profiling reveals differential responses to chronic nitrogen stress and putative nitrogen regulatory components in Arabidopsis , 2007, BMC Genomics.

[8]  Rafael A Irizarry,et al.  Exploration, normalization, and summaries of high density oligonucleotide array probe level data. , 2003, Biostatistics.

[9]  K. Vandepoele,et al.  Systematic Identification of Functional Plant Modules through the Integration of Complementary Data Sources1[W][OA] , 2012, Plant Physiology.

[10]  Y. Tsay,et al.  Arabidopsis Nitrate Transporter NRT1.9 Is Important in Phloem Nitrate Transport[W][OA] , 2011, Plant Cell.

[11]  A. Glass,et al.  A Reevaluation of the Role of Arabidopsis NRT1.1 in High-Affinity Nitrate Transport1 , 2013, Plant Physiology.

[12]  Homin K. Lee,et al.  Coexpression analysis of human genes across many microarray data sets. , 2004, Genome research.

[13]  Y. Tsay,et al.  The Arabidopsis Nitrate Transporter NRT1.7, Expressed in Phloem, Is Responsible for Source-to-Sink Remobilization of Nitrate[W][OA] , 2009, The Plant Cell Online.

[14]  Ruili Huang,et al.  Comprehensive analysis of pathway or functionally related gene expression in the National Cancer Institute's anticancer screen. , 2006, Genomics.

[15]  Andrew H. Beck,et al.  Importance of collection in gene set enrichment analysis of drug response in cancer cell lines , 2014, Scientific Reports.

[16]  N. Kolchanov,et al.  Abundances of microRNAs in human cells can be estimated as a function of the abundances of YRHB and RHHK tetranucleotides in these microRNAs as an ill-posed inverse problem solution , 2013, Front. Genet..

[17]  F. Sato,et al.  Nitrogen Recycling and Remobilization Are Differentially Controlled by Leaf Senescence and Development Stage in Arabidopsis under Low Nitrogen Nutrition1 , 2008, Plant Physiology.

[18]  Daniel A. Chamovitz,et al.  Large-scale analysis of Arabidopsis transcription reveals a basal co-regulation network , 2009, BMC Systems Biology.

[19]  Gabriel Krouk,et al.  A system biology approach highlights a hormonal enhancer effect on regulation of genes in a nitrate responsive "biomodule" , 2009, BMC Systems Biology.

[20]  A. Miller,et al.  TRANSPORTERS RESPONSIBLE FOR THE UPTAKE AND PARTITIONING OF NITROGENOUS SOLUTES. , 2001, Annual review of plant physiology and plant molecular biology.

[21]  M. Rossignol,et al.  Nitrate Efflux at the Root Plasma Membrane: Identification of an Arabidopsis Excretion Transporter[W] , 2007, The Plant Cell Online.

[22]  Eve Syrkin Wurtele,et al.  Articulation of three core metabolic processes in Arabidopsis: Fatty acid biosynthesis, leucine catabolism and starch metabolism , 2008, BMC Plant Biology.

[23]  Rodrigo A Gutiérrez,et al.  Systems approach identifies an organic nitrogen-responsive gene network that is regulated by the master clock control gene CCA1 , 2008, Proceedings of the National Academy of Sciences.

[24]  A. Gojon,et al.  Root uptake regulation: a central process for NPS homeostasis in plants. , 2009, Current opinion in plant biology.

[25]  Joshua M. Stuart,et al.  A Gene Expression Map for Caenorhabditis elegans , 2001, Science.

[26]  Joshua M. Stuart,et al.  A Gene-Coexpression Network for Global Discovery of Conserved Genetic Modules , 2003, Science.

[27]  S. Kopriva,et al.  Regulation of sulfate assimilation by nitrogen in Arabidopsis. , 2000, Plant physiology.

[28]  Yoshikazu Tanaka,et al.  Engineering of the rose flavonoid biosynthetic pathway successfully generated blue-hued flowers accumulating delphinidin. , 2007, Plant & cell physiology.

[29]  T. Ideker,et al.  Differential network biology , 2012, Molecular systems biology.

[30]  S. Bergmann,et al.  Similarities and Differences in Genome-Wide Expression Data of Six Organisms , 2003, PLoS biology.

[31]  Y. Tsay,et al.  Characterization of the Arabidopsis Nitrate Transporter NRT1.6 Reveals a Role of Nitrate in Early Embryo Development[W][OA] , 2008, The Plant Cell Online.

[32]  A. G. de la Fuente From 'differential expression' to 'differential networking' - identification of dysfunctional regulatory networks in diseases. , 2010, Trends in genetics : TIG.

[33]  Rongchen Wang,et al.  Microarray Analysis of the Nitrate Response in Arabidopsis Roots and Shoots Reveals over 1,000 Rapidly Responding Genes and New Linkages to Glucose, Trehalose-6-Phosphate, Iron, and Sulfate Metabolism1[w] , 2003, Plant Physiology.

[34]  Mark Gerstein,et al.  Large-scale atlas of microarray data reveals the distinct expression landscape of different tissues in Arabidopsis. , 2016, The Plant journal : for cell and molecular biology.

[35]  Francesca Chiaromonte,et al.  Qualitative network models and genome-wide expression data define carbon/nitrogen-responsive molecular machines in Arabidopsis , 2007, Genome Biology.

[36]  Gloria M Coruzzi,et al.  Genome-wide patterns of carbon and nitrogen regulation of gene expression validate the combined carbon and nitrogen (CN)-signaling hypothesis in plants , 2004, Genome Biology.

[37]  E. Marcotte,et al.  Systematic prediction of gene function in Arabidopsis thaliana using a probabilistic functional gene network , 2011, Nature Protocols.

[38]  A. Brazma,et al.  Reuse of public genome-wide gene expression data , 2012, Nature Reviews Genetics.

[39]  M. Tegeder Transporters for amino acids in plant cells: some functions and many unknowns. , 2012, Current opinion in plant biology.

[40]  G. Coruzzi,et al.  A unified nomenclature of NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER family members in plants. , 2014, Trends in plant science.

[41]  Nicholas J. Provart,et al.  An “Electronic Fluorescent Pictograph” Browser for Exploring and Analyzing Large-Scale Biological Data Sets , 2007, PloS one.

[42]  T. Kiba,et al.  The Arabidopsis Nitrate Transporter NRT2.4 Plays a Double Role in Roots and Shoots of Nitrogen-Starved Plants[C][W] , 2012, Plant Cell.

[43]  Mark Stitt,et al.  Genome-Wide Reprogramming of Primary and Secondary Metabolism, Protein Synthesis, Cellular Growth Processes, and the Regulatory Infrastructure of Arabidopsis in Response to Nitrogen1[w] , 2004, Plant Physiology.

[44]  M. Koshiba,et al.  Practical Quantum Cryptography: A Comprehensive Analysis (Part One) , 2000, quant-ph/0009027.

[45]  M. Palmgren PLANT PLASMA MEMBRANE H+-ATPases: Powerhouses for Nutrient Uptake. , 2001, Annual review of plant physiology and plant molecular biology.

[46]  D. Laird,et al.  Nitrogen fertilizer effects on soil carbon balances in midwestern U.S. agricultural systems. , 2009, Ecological applications : a publication of the Ecological Society of America.

[47]  Gabriel Krouk,et al.  A Systems View of Responses to Nutritional Cues in Arabidopsis: Toward a Paradigm Shift for Predictive Network Modeling1 , 2009, Plant Physiology.

[48]  Sean R. Davis,et al.  NCBI GEO: archive for functional genomics data sets—update , 2012, Nucleic Acids Res..

[49]  Y. Tsay,et al.  Nitrate transporters and peptide transporters , 2007, FEBS letters.

[50]  Paul G Falkowski,et al.  The Evolution and Future of Earth’s Nitrogen Cycle , 2010, Science.

[51]  E. Koonin,et al.  Conservation and coevolution in the scale-free human gene coexpression network. , 2004, Molecular biology and evolution.

[52]  B. Snel,et al.  The yeast coexpression network has a small‐world, scale‐free architecture and can be explained by a simple model , 2004, EMBO reports.

[53]  Sourav Bandyopadhyay,et al.  Rewiring of Genetic Networks in Response to DNA Damage , 2010, Science.

[54]  C. Lapierre,et al.  Evolution of a Novel Phenolic Pathway for Pollen Development , 2009, Science.

[55]  F. Daniel-Vedele,et al.  Nitrate transport in plants: which gene and which control? , 2002, Journal of experimental botany.

[56]  T. Martin,et al.  Short-term physiological and developmental responses to nitrogen availability in hybrid poplar. , 2005, The New phytologist.

[57]  Qin Ma,et al.  Genome-scale identification of cell-wall related genes in Arabidopsis based on co-expression network analysis , 2012, BMC Plant Biology.

[58]  T. Pawson,et al.  Selected reaction monitoring mass spectrometry reveals the dynamics of signaling through the GRB2 adaptor , 2011, Nature Biotechnology.

[59]  Dennis Shasha,et al.  A Systems Approach Uncovers Restrictions for Signal Interactions Regulating Genome-wide Responses to Nutritional Cues in Arabidopsis , 2009, PLoS Comput. Biol..

[60]  E. Grill,et al.  Stomatal Closure by Fast Abscisic Acid Signaling Is Mediated by the Guard Cell Anion Channel SLAH3 and the Receptor RCAR1 , 2011, Science Signaling.

[61]  Brian G Forde,et al.  Nitrogen regulation of root branching. , 2006, Annals of botany.

[62]  Y. Tsay,et al.  Uptake, allocation and signaling of nitrate. , 2012, Trends in plant science.

[63]  Alisdair R. Fernie,et al.  PLGG1, a plastidic glycolate glycerate transporter, is required for photorespiration and defines a unique class of metabolite transporters , 2013, Proceedings of the National Academy of Sciences.

[64]  N. Crawford,et al.  Proteins for Transport of Water and Mineral Nutrients across the Membranes of Plant Cells , 1999, Plant Cell.

[65]  N. Crawford,et al.  Dissection of the AtNRT2.1:AtNRT2.2 Inducible High-Affinity Nitrate Transporter Gene Cluster1[OA] , 2006, Plant Physiology.

[66]  Christopher S. Poultney,et al.  Insights into the genomic nitrate response using genetics and the Sungear Software System. , 2007, Journal of experimental botany.

[67]  Ulf-Ingo Flügge,et al.  The Plastidic Bile Acid Transporter 5 Is Required for the Biosynthesis of Methionine-Derived Glucosinolates in Arabidopsis thaliana[W] , 2009, The Plant Cell Online.

[68]  The role of CCoAOMT1 and COMT1 in Arabidopsis anthers , 2012, Planta.

[69]  G. Krouk,et al.  Nitrate signaling: adaptation to fluctuating environments. , 2010, Current opinion in plant biology.

[70]  T. Vogt,et al.  Evolutionarily conserved phenylpropanoid pattern on angiosperm pollen. , 2015, Trends in plant science.

[71]  K. Axelsen,et al.  Inventory of the superfamily of P-type ion pumps in Arabidopsis. , 2001, Plant physiology.

[72]  E. Marcotte,et al.  Prioritizing candidate disease genes by network-based boosting of genome-wide association data. , 2011, Genome research.

[73]  A. Fuente,et al.  From ‘differential expression’ to ‘differential networking’ – identification of dysfunctional regulatory networks in diseases , 2010 .

[74]  Julie A. Dickerson,et al.  Arabidopsis gene co-expression network and its functional modules , 2009, BMC Bioinformatics.

[75]  F. Daniel-Vedele,et al.  The Arabidopsis nitrate transporter NRT2.5 plays a role in nitrate acquisition and remobilization in nitrogen-starved plants. , 2014, The Plant journal : for cell and molecular biology.

[76]  S. Rhee,et al.  Towards revealing the functions of all genes in plants. , 2014, Trends in plant science.

[77]  Thomas Altmann,et al.  Variation of Enzyme Activities and Metabolite Levels in 24 Arabidopsis Accessions Growing in Carbon-Limited Conditions1[W] , 2006, Plant Physiology.

[78]  M. Ishii,et al.  [System biology]. , 2005, Nihon yakurigaku zasshi. Folia pharmacologica Japonica.

[79]  Angelo Andriulli,et al.  Loss of Connectivity in Cancer Co-Expression Networks , 2014, PloS one.

[80]  F. Daniel-Vedele,et al.  REVIEW: PART OF A SPECIAL ISSUE ON PLANT NUTRITION Nitrogen uptake, assimilation and remobilization in plants: challenges for sustainable and productive agriculture , 2010 .

[81]  Dong Xu,et al.  Pathway Correlation Profile of Gene-Gene Co-Expression for Identifying Pathway Perturbation , 2012, PloS one.