title: Inference of transcriptional networks in Arabidopsis through conserved noncoding sequence analysis.
abstract: Transcriptional regulation plays an important role in establishing gene expression profiles during development or in response to (a)biotic stimuli. Transcription factor binding sites (TFBSs) are the functional elements that determine transcriptional activity, and the identification of individual TFBS in genome sequences is a major goal to inferring regulatory networks. We have developed a phylogenetic footprinting approach for the identification of conserved noncoding sequences (CNSs) across 12 dicot plants. Whereas both alignment and non-alignment-based techniques were applied to identify functional motifs in a multispecies context, our method accounts for incomplete motif conservation as well as high sequence divergence between related species. We identified 69,361 footprints associated with 17,895 genes. Through the integration of known TFBS obtained from the literature and experimental studies, we used the CNSs to compile a gene regulatory network in Arabidopsis thaliana containing 40,758 interactions, of which two-thirds act through binding events located in DNase I hypersensitive sites. This network shows significant enrichment toward in vivo targets of known regulators, and its overall quality was confirmed using five different biological validation metrics. Finally, through the integration of detailed expression and function information, we demonstrate how static CNSs can be converted into condition-dependent regulatory networks, offering opportunities for regulatory gene annotation.
authors.affiliation: Department of Plant Systems Biology, VIB, B-9052 Ghent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, B-9052 Ghent, Belgium.
authors.forename: Jan
authors.identifier: http://orcid.org/0000-0001-7742-1266
authors.initials: J
authors.lastname: Van de Velde
authors.affiliation: Department of Plant Systems Biology, VIB, B-9052 Ghent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, B-9052 Ghent, Belgium.
authors.forename: Ken S
authors.identifier: http://orcid.org/0000-0001-5831-0536
authors.initials: KS
authors.lastname: Heyndrickx
authors.affiliation: Department of Plant Systems Biology, VIB, B-9052 Ghent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, B-9052 Ghent, Belgium klaas.vandepoele@psb.vib-ugent.be.
authors.forename: Klaas
authors.identifier: http://orcid.org/0000-0003-4790-2725
authors.initials: K
authors.lastname: Vandepoele
mesh_terms: D017360:Arabidopsis / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence / Q000235:genetics; D018744:DNA, Plant / Q000235:genetics; D018506:Gene Expression Regulation, Plant / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D018745:Genome, Plant / Q000235:genetics*; D023281:Genomics; D019684:Magnoliopsida / Q000235:genetics* / Q000378:metabolism; D059372:Nucleotide Motifs; D010802:Phylogeny; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods*; D026801:Synteny; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018744:DNA, Plant; D010940:Plant Proteins; D014157:Transcription Factors