Figure 6.

Through the superview analysis framework, we discovered previously known (A) and unknown (B) regulators for specific modules, as well as (C) novel edges for known regulators. (A) Cellulose synthase complexes (CSC) in COMc 36 are upregulated by MYB46. While MYB46 binds four module genes, the other regulators bind only one gene in the module. The module consists out of the primary cell wall CSC (CESA3, CESA1 and CESA6), the secondary cell wall CSC (CESA4, CESA7 and CESA8) and KOR1, a membrane-bound 1,4-β-D-glucanase (150,151). This module is tightly coexpressed in the abiotic stress compendium and upregulated upon brassinosteroid treatment (152) and salt stress conditions. COMc 36 has a significant ECD score under genotoxic, heat, oxidative and salt stress. In birch, overexpression mutants of MYB46 show thicker secondary cell walls and a higher tolerance to salt and osmotic stress (153). Cellulose synthases bind microtubules, hence stabilizing cellulose synthase localization at the plasma membrane and rendering plants less sensitive to salt stress (154). The relation between MYB46 and CSC is therefore important for the stress tolerance of crops. This example highlights the potential of integrating regulators with network motif modules. (B) The homeodomain TF CEH-30, which functions in neuronal cell fate and sex-specific apoptosis, was found to target a homolog group of heat shock proteins in worm. (C) CBF4 and ZML2 transcriptionally regulated the MYB/MYC module Atha COMc 48. The TFs MYB28, MYB29 and MYB76 control aliphatic glucosinolate biosynthesis (155), while MYB51 and MYB34 regulate indole glucosinolate biosynthesis (156). The JAZ-interacting TFs MYC2, MYC3 and MYC4 form together with the MYB TFs dimeric TF complexes to regulate the different glucosinolate biosynthesis pathways (95). Glucosinolates, a class of secondary metabolites mainly found in Brassicaceae, are part of a complex response to a variety of abiotic stresses. A decrease in aliphatic glucosinolates modifies the abundance of aquaporins and hence the water uptake in roots, thereby increasing drought and salt tolerance (157). Only the aliphatic glucosinolate biosynthesis TFs are directly bound by CBF4. In our abiotic stress compendium, we observed an upregulation of aliphatic glucosinolate biosynthesis (MYB26 and MYB76), indolic glucosinolate biosynthesis (MYB51), MYC2 and also of CBF4 upon salt stress; for MYB51 and CBF4 this is mostly in roots. It has been observed that CBF4 significantly alters the accumulation of at least five glucosinolates but the direct regulatory mechanism between CBF4 and glucosinolate synthesis has not been described (95). Here, we showed that the drought responsive gene cbf4 is an upstream regulator of the aliphatic glucosinolate biosynthesis which increases the tolerance to drought and salt stress. The function of zml2 in this context is still to be determined.