Qualitative network models and genome-wide expression data define carbon/nitrogen-responsive molecular machines in Arabidopsis

BackgroundCarbon (C) and nitrogen (N) metabolites can regulate gene expression in Arabidopsis thaliana. Here, we use multinetwork analysis of microarray data to identify molecular networks regulated by C and N in the Arabidopsis root system.ResultsWe used the Arabidopsis whole genome Affymetrix gene chip to explore global gene expression responses in plants exposed transiently to a matrix of C and N treatments. We used ANOVA analysis to define quantitative models of regulation for all detected genes. Our results suggest that about half of the Arabidopsis transcriptome is regulated by C, N or CN interactions. We found ample evidence for interactions between C and N that include genes involved in metabolic pathways, protein degradation and auxin signaling. To provide a global, yet detailed, view of how the cell molecular network is adjusted in response to the CN treatments, we constructed a qualitative multinetwork model of the Arabidopsis metabolic and regulatory molecular network, including 6,176 genes, 1,459 metabolites and 230,900 interactions among them. We integrated the quantitative models of CN gene regulation with the wiring diagram in the multinetwork, and identified specific interacting genes in biological modules that respond to C, N or CN treatments.ConclusionOur results indicate that CN regulation occurs at multiple levels, including potential post-transcriptional control by microRNAs. The network analysis of our systematic dataset of CN treatments indicates that CN sensing is a mechanism that coordinates the global and coordinated regulation of specific sets of molecular machines in the plant cell.

[1]  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.

[2]  M. Stitt,et al.  Nitrate regulation of metabolism and growth. , 1999, Current opinion in plant biology.

[3]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[4]  Ottoline Leyser,et al.  The Arabidopsis F-box protein TIR1 is an auxin receptor , 2005, Nature.

[5]  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.

[6]  Dennis Shasha,et al.  Fast Clustering and Minimum Weight Matching Algorithms for Very Large Mobile Backbone Wireless Networks , 2003, Int. J. Found. Comput. Sci..

[7]  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.

[8]  K. Koch CARBOHYDRATE-MODULATED GENE EXPRESSION IN PLANTS. , 1996, Annual review of plant physiology and plant molecular biology.

[9]  F. Daniel-Vedele,et al.  Molecular and functional regulation of two NO3- uptake systems by N- and C-status of Arabidopsis plants. , 1999, The Plant journal : for cell and molecular biology.

[10]  William N. Venables,et al.  S Programming , 2000 .

[11]  K. Forchhammer,et al.  Global carbon/nitrogen control by PII signal transduction in cyanobacteria: from signals to targets. , 2004, FEMS microbiology reviews.

[12]  Yves Gibon,et al.  Steps towards an integrated view of nitrogen metabolism. , 2002, Journal of experimental botany.

[13]  B. Forde Local and long-range signaling pathways regulating plant responses to nitrate. , 2002, Annual review of plant biology.

[14]  Lisa Schneper,et al.  Sense and sensibility: nutritional response and signal integration in yeast. , 2004, Current opinion in microbiology.

[15]  Rongchen Wang,et al.  Genomic Analysis of a Nutrient Response in Arabidopsis Reveals Diverse Expression Patterns and Novel Metabolic and Potential Regulatory Genes Induced by Nitrate , 2000, Plant Cell.

[16]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[17]  J. Lynch Root Architecture and Plant Productivity , 1995, Plant physiology.

[18]  L V Lejay,et al.  Adaptive combinatorial design to explore large experimental spaces: approach and validation. , 2004, Systems biology.

[19]  Gloria M Coruzzi,et al.  Genome-wide investigation of light and carbon signaling interactions in Arabidopsis , 2004, Genome Biology.

[20]  Peter Doerner,et al.  Arabidopsis TCP20 links regulation of growth and cell division control pathways. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Gloria Coruzzi,et al.  Genomic Analysis of the Nitrate Response Using a Nitrate Reductase-Null Mutant of Arabidopsis1[w] , 2004, Plant Physiology.

[22]  I. Graham,et al.  Arabidopsis Seedling Growth, Storage Lipid Mobilization, and Photosynthetic Gene Expression Are Regulated by Carbon:Nitrogen Availability1 , 2002, Plant Physiology.

[23]  Roland Arnold,et al.  MIPS Arabidopsis thaliana Database (MAtDB): an integrated biological knowledge resource based on the first complete plant genome , 2002, Nucleic Acids Res..

[24]  Ashverya Laxmi,et al.  Global Transcription Profiling Reveals Multiple Sugar Signal Transduction Mechanisms in Arabidopsis , 2004, The Plant Cell Online.

[25]  O. Massenet,et al.  Iron induces ferritin synthesis in maize plantlets , 1992, Plant Molecular Biology.

[26]  G. Bernier,et al.  The role of carbohydrates in the induction of flowering in Arabidopsis thaliana: comparison between the wild type and a starchless mutant , 1998, Planta.