Email updates

Keep up to date with the latest news and content from BMC Genomics and BioMed Central.

Open Access Research article

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

Christian Dubos123, Zsolt Kelemen12, Alvaro Sebastian4, Lorenz Bülow5, Gunnar Huep6, Wenjia Xu1, Damaris Grain1, Fabien Salsac1, Cecile Brousse1, Loïc Lepiniec1, Bernd Weisshaar6, Bruno Contreras-Moreira47 and Reinhard Hehl5*

  • * Corresponding author: Reinhard Hehl

  • † Equal contributors

Author Affiliations

1 INRA, Institut Jean-Pierre Bourgin, Saclay Plant Sciences, UMR1318, RD10, F-78026, Versailles, France

2 AgroParisTech, Institut Jean-Pierre Bourgin, Saclay Plant Sciences, UMR1318, RD10, F-78026, Versailles, France

3 Current address: Biochimie et Physiologie Moleculaire des Plantes, UMR 5004, INRA/CNRS/SupAgro-M/UM2, 34060 Montpellier Cedex 1, France

4 Estación Experimental de Aula Dei/CSIC, Av. Montañana 1.005, 50059 Zaragoza, Spain

5 Institut für Genetik, Technische Universität Braunschweig, Spielmannstr. 7, 38106 Braunschweig, Germany

6 Department of Biology, Bielefeld University, Universitaetsstrasse 25, 33615 Bielefeld, Germany

7 Fundación ARAID, calle María de Luna 11, 50018 Zaragoza, Spain

For all author emails, please log on.

BMC Genomics 2014, 15:317  doi:10.1186/1471-2164-15-317

Published: 28 April 2014



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.


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.


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.

Databases; Arabidopsis thaliana; Physcomitrella patens; Yeast one-hybrid; Microarray; Transcription factor; cis-element