Reverse engineering HD-Zip transcriptional regulatory networks (Ft. Information Theory)

ARCE, AGUSTIN L; CAPELLA, MATIAS; RE, DELFINA A; CHAN, RAQUEL L; CHERNOMORETZ, ARIEL

Oro Verde, Entre Rios

Congreso; III Congreso Argentino de Bioinformática y Biología Computacional; 2012

Background HD-Zip proteins constitute a family of plant transcription factors (TFs). It has been reported that proteins belonging to subfamilies I and II are mainly involved in responses to environmental stimuli, particularly abiotic stresses. However, the regulatory networks in which these TFs participate are largely unknown. In this work the transcriptional regulatory networks of Arabidopsis were reverse engineered employing algorithms based in information theory using public large scale transcriptomic assays. The results were analyzed from a functional and evolutionary point of view, focusing on HD-Zip I and II TFs. Materials and methods The program ARACNE was used for the network reconstruction. Filtered data consisted of 9618 genes and 269 microarrays obtained under different abiotic stress treatments (AtGenExpress project, http://www.weigelworld.org/resources/microarray/AtGenExpress/). As a result, sets of potential direct targets (named modules of transcriptional activity, MTAs) for each of the 831 TFs were obtained. Results The study of the MTAs of the 25 HD-Zip I and II TFs revealed many novel functional characteristics. A distinctive pattern of expression was found for subsets of genes in roots and shoots for most of the MTAs (e.g., MTA of AtHB1; Figure 1A). The overlap of the MTAs was more significant for some phylogenetically closely related genes (Figure 1B), suggesting a degree of functional redundancy in these cases. The expression correlation of the genes in each MTA under different stresses uncovered a potential unknown role for most TFs in heat response (e.g., AtHB12 MTA; Figure 1C). A de novo motif discovery approach on promoters of MTA genes with the support of conditional mutual information allowed the recognition of a potential interplay with GBF TFs. Functional studies with GO terms on MTA genes resulted in the association of the TFs with known and new pathways and functions. Arabidopsis HD-Zip mutants and overexpressors preliminary confirmed the predicted regulatory role for some TFs on selected genes. Other preliminary experimental data also supports their role in heat response.