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

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 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.

Vandepoele, K., Quimbaya, M., Casneuf, T., De Veylder, L., Van de Peer, Y. (2009) Unravelling transcriptional control in Arabidopsis using cis-regulatory elements and coexpression networks. Plant Physiol. 150(2):535-46.

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