A biophysical DNA binding model for the LEAFY transcription factor reveals the evolutionary fluidity of its binding sites

Despite great advances in sequencing capacity, generating functional information for non-model organisms remains a challenge. One solution lies in an improved ability to predict genetic circuits based on primary DNA sequence combined with the characterization of regulatory molecules from model species. Here, we focus on the LEAFY (LFY) transcription factor, a conserved master regulator of floral development. Starting with biochemical and structural information, we built a biophysical model describing LFY DNA binding specificity in vitro that accurately predicts in vivo LFY binding sites in the Arabidopsis thaliana genome. Extending the model to other species, we show that it can correctly identify functional homologs of known LFY targets from Arabidopsis thaliana in other angiosperms, even if a functional shift between orthologs and paralogs has occurred. Moreover, this model demonstrates the evolutionary fluidity of the link between LFY and one of its target genes, underlining how this regulatory interaction can be conserved despite changes in position, sequence and affinity of the LFY binding sites. Our study shows that the cis-element fluidity recently illustrated in animals also exists in plants, and that it can be detected without any experimental work in each individual species, using a biophysical transcription factor model. A. thaliana LEAFY ChIP-seq w control, 2 replicates