A functional and evolutionary perspective on transcription factor binding in Arabidopsis thaliana

Understanding the mechanisms underlying gene regulation is paramount to comprehend the translation from genotype to phenotype. The two are connected by gene expression, and it is generally thought that variation in transcription factor (TF) function is an important determinant of phenotypic evolution. We analysed publicly available genome-wide ChIP experiments for 27 transcription factors (TFs) in Arabidopsis thaliana and constructed an experimental network containing 46,619 regulatory interactions and 15,188 target genes. Hub targets and Highly Occupied Target (HOT) regions were identified, which are enriched for genes involved in development, stimuli response, signaling and gene regulatory processes in the currently profiled network. We provide several lines of evidence that TF binding at plant HOT regions is functional, in contrast to animals, and not merely the result of accessible chromatin. HOT regions harbor specific DNA motifs, are enriched for differentially expressed genes, are often conserved across crucifers and dicots, even though they are not under higher levels of purifying selection than non-HOT regions. Distal bound regions are under purifying selection as well, and are enriched for a chromatin state showing regulation by the Polycomb repressive complex. Gene expression complexity is positively correlated with the total number of regulating TFs, revealing insights in the regulatory code for genes with different expression breadths. The integration of non-canonical and canonical DNA motif information yields new hypotheses on co-binding and tethering between specific TFs involved in flowering and light regulation.

* Heyndrickx, KS., * Van de Velde, J., Wang, X., Weigel, D., Vandepoele, K. (2014) A functional and evolutionary perspective on transcription factor binding in Arabidopsis thaliana. The Plant Cell 26(10):3894-910. *contributed equally

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