A Systems Approach Uncovers Restrictions for Signal Interactions Regulating Genome-wide Responses to Nutritional Cues in Arabidopsis

As sessile organisms, plants must cope with multiple and combined variations of signals in their environment. However, very few reports have studied the genome-wide effects of systematic signal combinations on gene expression. Here, we evaluate a high level of signal integration, by modeling genome-wide expression patterns under a factorial combination of carbon (C), light (L), and nitrogen (N) as binary factors in two organs (O), roots and leaves. Signal management is different between C, N, and L and in shoots and roots. For example, L is the major factor controlling gene expression in leaves. However, in roots there is no obvious prominent signal, and signal interaction is stronger. The major signal interaction events detected genome wide in Arabidopsis roots are deciphered and summarized in a comprehensive conceptual model. Surprisingly, global analysis of gene expression in response to C, N, L, and O revealed that the number of genes controlled by a signal is proportional to the magnitude of the gene expression changes elicited by the signal. These results uncovered a strong constraining structure in plant cell signaling pathways, which prompted us to propose the existence of a “code” of signal integration.Author Summary: Light (L), nitrogen (N), and carbon (C) are well known to be strong signals regulating gene expression in plants. But, so far, few reports have described their interactions on a genome scale. Here, we report the transcriptome response of the factorial combination of these three signals in leaves and roots of Arabidopsis, corresponding to all possible combinations or 16 different treatment conditions. To mine this complete transcriptome data set, gene expression was modelled as a function of the C, N, L, and O (organ) signals. This computational approach revealed that multiple signals coordinate gene expression precisely and according to a constrained plan, which we call the “code of signal interaction.” Our studies indicated that signal integration occurs differently in different organs. We identified new modes of signal interaction that imply existence of new signaling pathways coordinating gene expression on a genomic scale.