Integrating bioinformatic resources to predict transcription factors interacting with cis-sequences conserved in co-regulated genes

Christian Dubos (1) , Zsolt Kelemen (1) , Alvaro Sebastian (2) , Lorenz Buelow (3) , Gunnar Huep (4) , Wenjia Xu (1) , Damaris Grain (1) , Fabien Salsac (1) , Cécile Brousse (1) , Loic Lepiniec (1) , Bernd Weisshaar (4) , Bruno Contreras-Moreira (2, 5) , Reinhard Hehl (3)

1 IJPB - Institut Jean-Pierre Bourgin
2 Estación Experimental de Aula Dei
3 Institut für Genetik
4 Department of Biology
5 ARAID - Fundación Agencia Aragonesa para la Investigación y el Desarrollo

Background: Using motif detection programs it is fairly straightforward to identify conserved cis-sequences in promoters of co-regulated genes. In contrast, the identification of the transcription factors (TFs) interacting with these cis-sequences is much more elaborate. To facilitate this, we explore the possibility of using several bioinformatic and experimental approaches for TF identification. This starts with the selection of co-regulated gene sets and leads first to the prediction and then to the experimental validation of TFs interacting with cis-sequences conserved in the promoters of these co-regulated genes. Results: Using the PathoPlant database, 32 up-regulated gene groups were identified with microarray data for drought-responsive gene expression from Arabidopsis thaliana. Application of the binding site estimation suite of tools (BEST) discovered 179 conserved sequence motifs within the corresponding promoters. Using the STAMP web-server, 49 sequence motifs were classified into 7 motif families for which similarities with known cis-regulatory sequences were identified. All motifs were subjected to a footprintDB analysis to predict interacting DNA binding domains from plant TF families. Predictions were confirmed by using a yeast-one-hybrid approach to select interacting TFs belonging to the predicted TF families. TF-DNA interactions were further experimentally validated in yeast and with a Physcomitrella patens transient expression system, leading to the discovery of several novel TF-DNA interactions. Conclusions: The present work demonstrates the successful integration of several bioinformatic resources with experimental approaches to predict and validate TFs interacting with conserved sequence motifs in co-regulated genes.

Mots clés: Databases; Arabidopsis thaliana; Physcomitrella patens; Yeast one-hybrid; Microarray; Transcription factor; cis-element; DNA-BINDING SPECIFICITY; ARABIDOPSIS-THALIANA; ABSCISIC-ACID; REGULATORY ELEMENTS; PROTEIN-BINDING; HYPOTHESIS GENERATION; INFORMATION RESOURCE; EXPRESSION ANALYSIS; PROMOTER ANALYSIS; STRESS RESPONSES

Domaines: Sciences du Vivant [q-bio]

Christian Dubos, Zsolt Kelemen, Alvaro Sebastian, Lorenz Buelow, Gunnar Huep, et al.. Integrating bioinformatic resources to predict transcription factors interacting with cis-sequences conserved in co-regulated genes. BMC Genomics, 2014, 15, ⟨10.1186/1471-2164-15-317⟩. ⟨hal-01204055⟩