The pan-cancer analysis of whole genomes The expansion of whole-genome sequencing studies from individual ICGC and TCGA working groups presented the opportunity to undertake a meta-analysis of genomic features across tumour types. To achieve this, the PCAWG Consortium was established. A Technical Working Group implemented the informatics analyses by aggregating the raw sequencing data from different working groups that studied individual tumour types, aligning the sequences to the human genome and delivering a set of high-quality somatic mutation calls for downstream analysis (Extended Data Fig. 1). Given the recent meta-analysis

The symbiotic association of legumes with rhizobia involves bacterially derived Nod factor, which is sufficient to activate the formation of nodules on the roots of the host plant. Perception of Nod factor by root hair cells induces calcium oscillations that are a component of the Nod factor signal transduction pathway. Perception of the calcium oscillations is a function of a calcium-and calmodulin-dependent protein kinase, and this activates nodulation gene expression via two GRAS domain transcriptional regulators, Nodulation Signaling Pathway1 (NSP1) and NSP2, and an ERF transcription factor required for nodulation. Here, we show that NSP1 and NSP2 form a complex that is associated with the promoters of early nodulin genes. We show that NSP1 binds directly to ENOD promoters through the novel cis-element AATTT. While NSP1 shows direct binding to the ENOD11 promoter in vitro, this association in vivo requires NSP2. The NSP1-NSP2 association with the ENOD11 promoter is enhanced following Nod factor elicitation. Mutations in the domain of NSP2 responsible for its interaction with NSP1 highlight the significance of the NSP1-NSP2 heteropolymer for nodulation signaling. Our work reveals direct binding of a GRAS protein complex to DNA and highlights the importance of the NSP1-NSP2 complex for efficient nodulation in the model legume Medicago truncatula.

Legumes, such as Medicago truncatula, form mutualistic symbiotic relationships with nitrogen-fixing rhizobial bacteria. This occurs within specialized root organs--nodules--that provide the conditions required for nitrogen fixation. A rhizobium-derived signalling molecule, Nod factor, is required to establish the symbiosis. Perception of Nod factor in the plant leads to the induction of Ca2+ oscillations, and the transduction of this Ca2+ signal requires DMI3 (refs 2, 3), which encodes the protein kinase Ca2+/calmodulin-dependent protein kinase (CCaMK). Central to the regulation of CCaMK is an autoinhibitory domain that negatively regulates kinase activity. Here we show that the specific removal of the autoinhibition domain leads to the autoactivation of the nodulation signalling pathway in the plant, with the resultant induction of nodules and nodulation gene expression in the absence of bacterial elicitation. This autoactivation requires nodulation-specific transcriptional regulators in the GRAS family. This work demonstrates that the release of autoinhibition from CCaMK after calmodulin binding is a central switch that is sufficient to activate nodule morphogenesis. The fact that a single regulation event is sufficient to induce nodulation highlights the possibility of transferring this process to non-legumes.

SUMMARYTwo different gene families have been proposed to act as sorting receptors for vacuolar storage cargo in plants: the vacuolar sorting receptors (VSRs) and the receptor homology-transmembrane-RING H2 domain proteins (RMRs). However, functional data on these genes is scarce and the identity of the sorting receptor for storage proteins remains controversial. Through a genetic screen we have identified the mtv2 mutant, which is defective in vacuolar transport of the storage cargo VAC2 in shoot apices. Map-based cloning revealed that mtv2 is a loss of function allele of the VSR4 gene. We show that VSR1, VSR3 and VSR4, but not the remaining VSRs or RMRs, participate in vacuolar sorting of VAC2 in vegetative tissues, and 12S globulins and 2S albumins in seeds, an activity that is essential for seedling germination vigor. Finally, we demonstrate that the functional diversification in the VSR family results from divergent expression patterns and also from distinct sorting activities of the family members.