ARACNe-based inference, using curated microarray data, of Arabidopsis thaliana root transcriptional regulatory networks

BackgroundUncovering the complex transcriptional regulatory networks (TRNs) that underlie plant and animal development remains a challenge. However, a vast amount of data from public microarray experiments is available, which can be subject to inference algorithms in order to recover reliable TRN architectures.ResultsIn this study we present a simple bioinformatics methodology that uses public, carefully curated microarray data and the mutual information algorithm ARACNe in order to obtain a database of transcriptional interactions. We used data from Arabidopsis thaliana root samples to show that the transcriptional regulatory networks derived from this database successfully recover previously identified root transcriptional modules and to propose new transcription factors for the SHORT ROOT/SCARECROW and PLETHORA pathways. We further show that these networks are a powerful tool to integrate and analyze high-throughput expression data, as exemplified by our analysis of a SHORT ROOT induction time-course microarray dataset, and are a reliable source for the prediction of novel root gene functions. In particular, we used our database to predict novel genes involved in root secondary cell-wall synthesis and identified the MADS-box TF XAL1/AGL12 as an unexpected participant in this process.ConclusionsThis study demonstrates that network inference using carefully curated microarray data yields reliable TRN architectures. In contrast to previous efforts to obtain root TRNs, that have focused on particular functional modules or tissues, our root transcriptional interactions provide an overview of the transcriptional pathways present in Arabidopsis thaliana roots and will likely yield a plethora of novel hypotheses to be tested experimentally.

[1]  D. Delmer,et al.  TRICHOME BIREFRINGENCE and Its Homolog AT5G01360 Encode Plant-Specific DUF231 Proteins Required for Cellulose Biosynthesis in Arabidopsis1[W][OA] , 2010, Plant Physiology.

[2]  J. Ripoll,et al.  Alteration of the shoot radial pattern in Arabidopsis thaliana by a gain-of-function allele of the class III HD-Zip gene INCURVATA4. , 2008, The International journal of developmental biology.

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

[4]  T. Demura,et al.  Primary phloem-specific expression of a Zinnia elegans homeobox gene. , 2001, Plant & cell physiology.

[5]  Yann LeCun,et al.  Predictive network modeling of the high-resolution dynamic plant transcriptome in response to nitrate , 2010, Genome Biology.

[6]  Eugenio Azpeitia,et al.  Single-cell and coupled GRN models of cell patterning in the Arabidopsis thaliana root stem cell niche , 2010, BMC Systems Biology.

[7]  E. Álvarez-Buylla,et al.  An AGAMOUS-Related MADS-Box Gene, XAL1 (AGL12), Regulates Root Meristem Cell Proliferation and Flowering Transition in Arabidopsis1[W][OA] , 2008, Plant Physiology.

[8]  I. Somssich,et al.  Transcriptional reprogramming regulated by WRKY18 and WRKY40 facilitates powdery mildew infection of Arabidopsis. , 2010, The Plant journal : for cell and molecular biology.

[9]  Trey Ideker,et al.  Cytoscape 2.8: new features for data integration and network visualization , 2010, Bioinform..

[10]  R. Zhong,et al.  Global analysis of direct targets of secondary wall NAC master switches in Arabidopsis. , 2010, Molecular plant.

[11]  T. Demura,et al.  Identifying New Components Participating in the Secondary Cell Wall Formation of Vessel Elements in Zinnia and Arabidopsis[W] , 2009, The Plant Cell Online.

[12]  J. Kim,et al.  The AtGRF family of putative transcription factors is involved in leaf and cotyledon growth in Arabidopsis. , 2003, The Plant journal : for cell and molecular biology.

[13]  James A.H. Murray,et al.  A Bistable Circuit Involving SCARECROW-RETINOBLASTOMA Integrates Cues to Inform Asymmetric Stem Cell Division , 2012, Cell.

[14]  S. Balzergue,et al.  Disruption of LACCASE4 and 17 Results in Tissue-Specific Alterations to Lignification of Arabidopsis thaliana Stems[W] , 2011, Plant Cell.

[15]  J. A. Buso,et al.  BMC Plant Biology , 2003 .

[16]  Teva Vernoux,et al.  An Evolutionarily Conserved Mechanism Delimiting SHR Movement Defines a Single Layer of Endodermis in Plants , 2007, Science.

[17]  Philip N. Benfey,et al.  Mechanisms Regulating SHORT-ROOT Intercellular Movement , 2004, Current Biology.

[18]  R. Zhong,et al.  A Battery of Transcription Factors Involved in the Regulation of Secondary Cell Wall Biosynthesis in Arabidopsis , 2008, The Plant Cell Online.

[19]  T. Demura,et al.  VASCULAR-RELATED NAC-DOMAIN6 and VASCULAR-RELATED NAC-DOMAIN7 Effectively Induce Transdifferentiation into Xylem Vessel Elements under Control of an Induction System1[W] , 2010, Plant Physiology.

[20]  D. Weijers,et al.  A cellular expression map of the Arabidopsis AUXIN RESPONSE FACTOR gene family. , 2011, The Plant journal : for cell and molecular biology.

[21]  Adam A. Margolin,et al.  Reverse engineering cellular networks , 2006, Nature Protocols.

[22]  Takashi Aoyama,et al.  A Genetic Framework for the Control of Cell Division and Differentiation in the Root Meristem , 2008, Science.

[23]  C. Haigler,et al.  Cysteine proteases XCP1 and XCP2 aid micro-autolysis within the intact central vacuole during xylogenesis in Arabidopsis roots. , 2008, The Plant journal : for cell and molecular biology.

[24]  T. Umezawa,et al.  Characterization of Arabidopsis thaliana Pinoresinol Reductase, a New Type of Enzyme Involved in Lignan Biosynthesis* , 2008, Journal of Biological Chemistry.

[25]  P. Zimmermann,et al.  Genome-Scale Proteomics Reveals Arabidopsis thaliana Gene Models and Proteome Dynamics , 2008, Science.

[26]  T. Demura,et al.  VND-INTERACTING2, a NAC Domain Transcription Factor, Negatively Regulates Xylem Vessel Formation in Arabidopsis[W][OA] , 2010, Plant Cell.

[27]  Di Liu,et al.  DATF: a database of Arabidopsis transcription factors , 2005, Bioinform..

[28]  Yuji Kamiya,et al.  Transcription factor AtTCP14 regulates embryonic growth potential during seed germination in Arabidopsis thaliana. , 2008, The Plant journal : for cell and molecular biology.

[29]  David J. Craigon,et al.  Using genomic DNA-based probe-selection to improve the sensitivity of high-density oligonucleotide arrays when applied to heterologous species , 2005, Plant Methods.

[30]  Chris Wiggins,et al.  ARACNE: An Algorithm for the Reconstruction of Gene Regulatory Networks in a Mammalian Cellular Context , 2004, BMC Bioinformatics.

[31]  Ykä Helariutta,et al.  A Mutually Inhibitory Interaction between Auxin and Cytokinin Specifies Vascular Pattern in Roots , 2011, Current Biology.

[32]  C. Hardtke,et al.  Flowering as a Condition for Xylem Expansion in Arabidopsis Hypocotyl and Root , 2008, Current Biology.

[33]  Lonnie R. Welch,et al.  AGRIS: the Arabidopsis Gene Regulatory Information Server, an update , 2010, Nucleic Acids Res..

[34]  Olivier Voinnet,et al.  LOST MERISTEMS genes regulate cell differentiation of central zone descendants in Arabidopsis shoot meristems. , 2010, The Plant journal : for cell and molecular biology.

[35]  J. Colasanti,et al.  Activity of transcription factor JACKDAW is essential for SHR/SCR-dependent activation of SCARECROW and MAGPIE and is modulated by reciprocal interactions with MAGPIE, SCARECROW and SHORT ROOT , 2011, Plant Molecular Biology.

[36]  Jonathan D. G. Jones,et al.  Evidence for Network Evolution in an Arabidopsis Interactome Map , 2011, Science.

[37]  Chuanyou Li,et al.  The bHLH-type transcription factor AtAIB positively regulates ABA response in Arabidopsis , 2007, Plant Molecular Biology.

[38]  I. Somssich,et al.  Nuclear Activity of MLA Immune Receptors Links Isolate-Specific and Basal Disease-Resistance Responses , 2007, Science.

[39]  Vipin T. Sreedharan,et al.  Multiple reference genomes and transcriptomes for Arabidopsis thaliana , 2011, Nature.

[40]  Audrey Kauffmann,et al.  Bioinformatics Applications Note Arrayqualitymetrics—a Bioconductor Package for Quality Assessment of Microarray Data , 2022 .

[41]  Laura Ragni,et al.  Spatio-temporal sequence of cross-regulatory events in root meristem growth , 2010, Proceedings of the National Academy of Sciences.

[42]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[43]  Adam A. Margolin,et al.  Reverse engineering of regulatory networks in human B cells , 2005, Nature Genetics.

[44]  P. Benfey,et al.  Mutations affecting the radial organisation of the Arabidopsis root display specific defects throughout the embryonic axis , 1995 .

[45]  Zhang-liang Chen,et al.  Identification and characterization of COI1-dependent transcription factor genes involved in JA-mediated response to wounding in Arabidopsis plants , 2007, Plant Cell Reports.

[46]  F. Ferrari,et al.  The Reconstruction of Transcriptional Networks Reveals Critical Genes with Implications for Clinical Outcome of Multiple Myeloma , 2011, Clinical Cancer Research.

[47]  Philip N Benfey,et al.  Both the conserved GRAS domain and nuclear localization are required for SHORT-ROOT movement. , 2009, The Plant journal : for cell and molecular biology.

[48]  B. Sundberg,et al.  Walls are thin 1 (WAT1), an Arabidopsis homolog of Medicago truncatula NODULIN21, is a tonoplast-localized protein required for secondary wall formation in fibers. , 2010, The Plant journal : for cell and molecular biology.

[49]  S. Wi,et al.  Mutation of the chitinase-like protein-encoding AtCTL2 gene enhances lignin accumulation in dark-grown Arabidopsis seedlings. , 2010, Journal of plant physiology.

[50]  Dominique C Bergmann,et al.  Regulation of the Arabidopsis root vascular initial population by LONESOME HIGHWAY , 2007, Development.

[51]  R. Amasino,et al.  The PLETHORA Genes Mediate Patterning of the Arabidopsis Root Stem Cell Niche , 2004, Cell.

[52]  M. Aluru,et al.  A brassinosteroid transcriptional network revealed by genome-wide identification of BESI target genes in Arabidopsis thaliana. , 2011, The Plant journal : for cell and molecular biology.

[53]  T. Demura,et al.  VASCULAR-RELATED NAC-DOMAIN7 directly regulates the expression of a broad range of genes for xylem vessel formation. , 2011, The Plant journal : for cell and molecular biology.

[54]  J. J. Taylor,et al.  Disruption of interfascicular fiber differentiation in an Arabidopsis mutant. , 1997, The Plant cell.

[55]  Peter Widmayer,et al.  Genevestigator V3: A Reference Expression Database for the Meta-Analysis of Transcriptomes , 2008, Adv. Bioinformatics.

[56]  K. Palme,et al.  The Basic Helix-Loop-Helix Transcription Factor MYC2 Directly Represses PLETHORA Expression during Jasmonate-Mediated Modulation of the Root Stem Cell Niche in Arabidopsis[W][OA] , 2011, Plant Cell.

[57]  Masakazu Satou,et al.  RARTF: database and tools for complete sets of Arabidopsis transcription factors. , 2005, DNA research : an international journal for rapid publication of reports on genes and genomes.

[58]  G. Coupland,et al.  The Arabidopsis SOC1-like genes AGL42, AGL71 and AGL72 promote flowering in the shoot apical and axillary meristems. , 2011, The Plant journal : for cell and molecular biology.

[59]  Masayuki Higuchi,et al.  Cytokinin Signaling and Its Inhibitor AHP6 Regulate Cell Fate During Vascular Development , 2006, Science.

[60]  Gary D Bader,et al.  Enrichment Map: A Network-Based Method for Gene-Set Enrichment Visualization and Interpretation , 2010, PloS one.

[61]  Srilakshmi Makkena,et al.  The bHLH transcription factor SPATULA regulates root growth by controlling the size of the root meristem , 2013, BMC Plant Biology.

[62]  Andrea Califano,et al.  Integrated biochemical and computational approach identifies BCL6 direct target genes controlling multiple pathways in normal germinal center B cells. , 2008, Blood.

[63]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[64]  J. Pittman,et al.  Elucidating the Mechanisms of Assembly and Subunit Interaction of the Cellulose Synthase Complex of Arabidopsis Secondary Cell Walls* , 2009, Journal of Biological Chemistry.

[65]  Rafael A. Irizarry,et al.  A Model-Based Background Adjustment for Oligonucleotide Expression Arrays , 2004 .

[66]  S. Sabatini,et al.  SCARECROW is involved in positioning the stem cell niche in the Arabidopsis root meristem. , 2003, Genes & Development.

[67]  J. Ecker,et al.  Three redundant brassinosteroid early response genes encode putative bHLH transcription factors required for normal growth. , 2002, Genetics.

[68]  Rosangela Sozzani,et al.  Arabidopsis Homologs of the Petunia HAIRY MERISTEM Gene Are Required for Maintenance of Shoot and Root Indeterminacy1[C][W][OA] , 2010, Plant Physiology.

[69]  Renze Heidstra,et al.  PLETHORA proteins as dose-dependent master regulators of Arabidopsis root development , 2007, Nature.

[70]  K. Mutsumi [Transcription factor database]. , 2004, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[71]  T. Demura,et al.  Vascular-related NAC-DOMAIN7 is involved in the differentiation of all types of xylem vessels in Arabidopsis roots and shoots. , 2008, The Plant journal : for cell and molecular biology.

[72]  C. Douglas,et al.  OVATE FAMILY PROTEIN4 (OFP4) interaction with KNAT7 regulates secondary cell wall formation in Arabidopsis thaliana. , 2011, The Plant journal : for cell and molecular biology.

[73]  P. Bauer,et al.  Iron deficiency-mediated stress regulation of four subgroup Ib BHLH genes in Arabidopsis thaliana , 2007, Planta.

[74]  W. Gruissem,et al.  pep2pro: a new tool for comprehensive proteome data analysis to reveal information about organ-specific proteomes in Arabidopsis thaliana. , 2011, Integrative biology : quantitative biosciences from nano to macro.

[75]  Y. Helariutta,et al.  Sending mixed messages: auxin-cytokinin crosstalk in roots. , 2011, Current opinion in plant biology.

[76]  Molly Megraw,et al.  A stele-enriched gene regulatory network in the Arabidopsis root , 2011, Molecular systems biology.

[77]  Ben Lehner,et al.  Evolutionary plasticity of genetic interaction networks , 2008, Nature Genetics.

[78]  Hitoshi Sakakibara,et al.  Genome-Wide Direct Target Analysis Reveals a Role for SHORT-ROOT in Root Vascular Patterning through Cytokinin Homeostasis1[W][OA] , 2011, Plant Physiology.

[79]  Kengo Kinoshita,et al.  ATTED-II Updates: Condition-Specific Gene Coexpression to Extend Coexpression Analyses and Applications to a Broad Range of Flowering Plants , 2011, Plant & cell physiology.

[80]  P. Benfey,et al.  Whole-Genome Analysis of the SHORT-ROOT Developmental Pathway in Arabidopsis , 2006, PLoS biology.

[81]  R. Irizarry,et al.  A gene expression bar code for microarray data , 2007, Nature Methods.

[82]  Tetsuro Mimura,et al.  Transcription switches for protoxylem and metaxylem vessel formation. , 2005, Genes & development.

[83]  M. Ibañes,et al.  Brassinosteroid signaling and auxin transport are required to establish the periodic pattern of Arabidopsis shoot vascular bundles , 2009, Proceedings of the National Academy of Sciences.

[84]  Wolfgang Busch,et al.  The bHLH Transcription Factor POPEYE Regulates Response to Iron Deficiency in Arabidopsis Roots[W][OA] , 2010, Plant Cell.

[85]  R. Zhong,et al.  The MYB46 Transcription Factor Is a Direct Target of SND1 and Regulates Secondary Wall Biosynthesis in Arabidopsis , 2007, The Plant Cell Online.

[86]  Staffan Persson,et al.  The Arabidopsis irregular xylem8 Mutant Is Deficient in Glucuronoxylan and Homogalacturonan, Which Are Essential for Secondary Cell Wall Integrity[W] , 2007, The Plant Cell Online.

[87]  P. Benfey,et al.  Root development in Arabidopsis: four mutants with dramatically altered root morphogenesis. , 1993, Development.

[88]  Hans Meinhardt,et al.  Auxin triggers a genetic switch , 2011, Nature Cell Biology.

[89]  Mark Stitt,et al.  Real-time RT-PCR profiling of over 1400 Arabidopsis transcription factors: unprecedented sensitivity reveals novel root- and shoot-specific genes. , 2004, The Plant journal : for cell and molecular biology.

[90]  Cole Trapnell,et al.  Ultrafast and memory-efficient alignment of short DNA sequences to the human genome , 2009, Genome Biology.

[91]  H. Fukuda,et al.  Arabidopsis VASCULAR-RELATED NAC-DOMAIN6 Directly Regulates the Genes That Govern Programmed Cell Death and Secondary Wall Formation during Xylem Differentiation[C][W] , 2010, Plant Cell.

[92]  Renze Heidstra,et al.  Arabidopsis JACKDAW and MAGPIE zinc finger proteins delimit asymmetric cell division and stabilize tissue boundaries by restricting SHORT-ROOT action. , 2007, Genes & development.

[93]  P. Benfey,et al.  Spatiotemporal regulation of cell-cycle genes by SHORTROOT links patterning and growth , 2010, Nature.

[94]  Enrico Scarpella,et al.  Regulation of preprocambial cell state acquisition by auxin signaling in Arabidopsis leaves , 2009, Development.

[95]  T. Altmann,et al.  Brassinosteroids Promote Root Growth in Arabidopsis , 2003, Plant Physiology.

[96]  R. Zhong,et al.  MYB83 is a direct target of SND1 and acts redundantly with MYB46 in the regulation of secondary cell wall biosynthesis in Arabidopsis. , 2009, Plant & cell physiology.