Plant Physiol. Journal of Pharmacology and Experimental Therapeutics
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Published on April 8, 2009; 10.1104/pp.109.136028

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Received January 22, 2009
Accepted April 2, 2009

Unraveling transcriptional control in Arabidopsis using cis-regulatory elements and coexpression networks

Klaas Vandepoele , Mauricio Quimbaya , Tine Casneuf , Lieven De Veylder , and Yves Van de Peer *

Department of Plant Systems Biology, VIB, Technologiepark 927, B-9052 Ghent, Belgium. Department of Molecular Genetics, Ghent University, Technologiepark 927, B-9052 Ghent, Belgium

* Corresponding author; email: yves.vandepeer{at}psb.ugent.be.

Analysis of gene expression data generated by high-throughput microarray transcript profiling experiments has demonstrated that genes with an overall similar expression pattern are often enriched for similar functions. This guilt-by-association principle can be applied to define modular gene programs, identify cis-regulatory elements or predict gene functions for unknown genes based on their coexpression neighborhood. We evaluated the potential to use Gene Ontology (GO) enrichment of a gene's coexpression neighborhood as a tool to predicts its function but found overall low sensitivity scores (13-34%). This indicates that for many functional categories coexpression alone performs poorly to infer known biological gene functions. However, integration of cis-regulatory elements shows that 46% of the gene coexpression neighborhoods are enriched for one or more motif, providing a valuable complementary source to functionally annotate genes. Through the integration of coexpression data, GO annotations and a set of known cis-regulatory elements combined with a novel set of evolutionary conserved plant motifs, we could link many genes and motifs to specific biological functions. Application of our coexpression framework extended with cis-regulatory element analysis on transcriptome data from the cell cycle-related transcription factor OBP1 yielded several coexpressed modules associated with specific cis-regulatory elements. Moreover, our analysis strongly suggests a feed forward regulatory interaction between OBP1 and the E2F pathway. The ATCOECIS resource (http://bioinformatics.psb.ugent.be/ATCOECIS/) makes it possible to query coexpression data, GO and cis-regulatory elements annotations, submit user-defined gene sets for motif analysis and provides an access point to unravel the regulatory code underlying transcriptional control in Arabidopsis.






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