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BIOINFORMATICS

Unraveling Transcriptional Control in Arabidopsis Using cis-Regulatory Elements and Coexpression Networks^1,[C],[W]

Department of Plant Systems Biology, Flanders Institute for Biotechnology, B–9052 Ghent, Belgium; and Department of Plant Biotechnology and Genetics, Ghent University, B–9052 Ghent, Belgium

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 predict 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 motifs, 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 evolutionarily 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 and GO and cis-regulatory element annotations and to submit user-defined gene sets for motif analysis, providing an access point to unravel the regulatory code underlying transcriptional control in Arabidopsis (Arabidopsis thaliana).

² Present address: Ortho Biotech Oncology Research and Development, a division of Janssen Pharmaceutica, Turnhoutseweg 30, B–2340 Beerse, Belgium.

The author responsible for the distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantphysiol.org) is: Yves Van de Peer (yves.vandepeer{at}psb.ugent.be).

^[C] Some figures in this article are displayed in color online but in black and white in the print edition.

^[W] The online version of this article contains Web-only data.

www.plantphysiol.org/cgi/doi/10.1104/pp.109.136028

^* Corresponding author; e-mail yves.vandepeer{at}psb.ugent.be.

Received January 22, 2009; accepted April 2, 2009; published April 8, 2009.