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

AuthorsDubos, Christian; Kelemen, Zsolt; Sebastián Yagüe, Álvaro CSIC; Bülow, Lorenz; Huep, Gunnar; Xu, Wenjia; Grain, Damaris; Salsac, Fabien; Brousse, Cecile; Lepiniec, Löic; Weisshaar, Bernd; Contreras-Moreira, Bruno CSIC ORCID ; Hehl, Reinhard
Arabidopsis thaliana
Physcomitrella patens
Yeast one-hybrid
Transcription factor
Issue Date28-Apr-2014
PublisherBioMed Central
CitationBMC Genomics 15(1): 317 (2014)
Abstract[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.
DescriptionThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
Publisher version (URL)http://dx.doi.org/10.1186/1471-2164-15-317
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