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Cracking the code of transcriptional regulation: the key to the past and future evolution of plants – Plant-TFcode

Submission summary

We propose to quantitatively model the interactions between four plant transcription factors (TFs) and their direct target genes, and to use the model generated to better understand existing plant biodiversity and to attempt the rational modification of plant characteristics. Networks of transcriptional regulation play an essential role in the development of living organisms. Similar sets of genes may generate very different biological structures, depending on the nature of their network interactions. In plants, TFs represent a significant percentage of the genome, and their key roles in many developmental processes are well-documented. Subtle changes to TFs have recently been shown to have been responsible for the advantageous characteristics selected by man during the domestication of the major cereal crops. The 'systems biology' approach aims to model complex systems. To use this approach, it is essential to first identify the factors of key importance in the system under study, and then to characterise their interactions. In the case of transcriptional regulatory networks, systems biology requires the characterisation of interactions between TFs, and between TFs and the cis-regulatory regions of their target genes. Our project will model the interactions between four key plant, developmental TFs and their target genes. We have chosento study four factors: LFY, CRC, LEC2 and WRI1, belonging to four different plant-specific classes, which act in the three successive processes of: flower (LFY), carpel (CRC) and seed (LEC2 and WRI1) development. Direct target genes are known for each of these TFs, in part through our own previous studies. Our project has three major objectives: • To provide a deep and quantitative understanding of the biochemical interactions of four plant-specific TFs in the present-day model plant Arabidopsis thaliana. • To understand the past roles that these four TFs played to generate present-day biodiversity, both at an intra-specific level in A. thaliana, and at a macro-evolutionary level throughout the flowering plants. • To prove that we can modify plant form in subtle and useful ways using the knowledge of TFs that we will obtain over the course of this project. To achieve these objectives, we will first use innovative biophysical and biochemical methods to characterise interactions between TFs and their target sequences in present-day A. thaliana. Target DNA motifs will be studied both in their isolated form, and within the context of whole promoters. Our strategy will generate a powerful tool to predict TF-DNA binding interactions that will take into account binding specificities, binding site numbers, and cooperative binding to gene promoters. Secondly, we will investigate the past importance of changes to biochemical interactions involving the four TFs to evolutionary processes at the two different time-scales that generated: (1) intra-specific differences between different A. thaliana accessions, and (2) major evolutionary differences within the entire flowering plant clade. This latter analysis will involve comparisons between A. thaliana and Amborella trichopoda, which is the most basal living angiosperm: the sister to all other flowering plant species. Thirdly, we will apply the lessons learned from the study of crop domestication, in addition to insights obtained in the initial stages of this project, to attempt the directed modification of plants by modifying interactions between TFs and their target genes. This 'proof-of-concept' experiment of 'targeted domestication' should be of immense interest to the plant science community, as we expect it to demonstrate the feasibility of a novel form of plant improvement that will not require the introduction of 'foreign' DNA into the plant. This latter aspect may result in greater public acceptance for our technology, compared to classic transgenic approaches. Our project represents a close collaboration between three research teams with highly complementary expertise in the analysis of TFs. We will particularly exploit novel biophysical and biochemical techniques to model the interactions between TFs and their target promoters. We expect our project to significantly improve the depth of understanding of transcriptional interactions in plants. It should also constitute a major leap-forward in our understanding of the molecular differences that underlie present-day plant biodiversity, and furthermore provide us with a subtle and powerful means to modify plant traits for the future.

Project coordination

Francois Parcy (Organisme de recherche)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Help of the ANR 460,000 euros
Beginning and duration of the scientific project: - 48 Months

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