In every organism, the expression of genes is regulated in response to the changes in the surrounding environment. The study of epigenetics in plants is essential in view of the improvement of agricultural productivity. Epigenetic modifications can enhance crops’ yield and stress tolerance without making any alteration within their genomic sequences. The routes of epigenetic modifications include processes such as methylation of DNA, modifications of histone proteins, chromatin remodeling, and non-coding RNA-mediated regulation of genes. Genome-wide epigenetic profiles, coined as the epigenome, of several plants have been identified in recent years. In the scope of this review, we are going to discuss progress made in the field of plant epigenomics under the limelight of stress tolerance, especially saline conditions.

Cells perceive and respond to the extracellular matrix (ECM)viaintegrin receptors; their dysregulation has been implicated in inflammation and cancer metastasis. Here we show that a guanine nucleotide exchange modulator of trimeric-GTPase Gαi, GIV (a.k.aGirdin), directly binds the integrin adaptor Kindlin-2. A non-canonical short linear motif within GIV’s C-terminus binds Kindlin-2-FERM3 domain at a site that is distinct from the binding site for the canonical NPxY motif on the -integrin tail. Binding of GIV to Kindlin-2 allosterically enhances Kindlin-2’s affinity for β1-integrin. Consequently, integrin activation and clustering are maximized, which augments cell adhesion, spreading and invasion. Findings elucidate how the GIV•Kindlin-2 complex has a two-fold impact: it allosterically synergizes integrin activation and enables β1-integrins to indirectly access and modulate trimeric GTPasesviathe complex. Furthermore, Cox proportional-hazard models on tumor transcriptomics provide trans-scale evidence of synergistic interactions between GIV•Kindlin-2•β1-integrin on time to progression to metastasis.The eTOC blurb: Integrins mediate cell adhesion to the extracellular matrix; their dysregulation fuels inflammation, cancer cell invasion and metastasis. Authors show how two pro-metastatic scaffold proteins, Kindlin and GIV/Girdin bind and cooperatively enhance their allosteric coupling to integrins, and their subsequent activation. Findings reveal novel interfaces in integrin signaling for pharmacologic manipulation.HIGHLIGHTS: GIV and Kindlin(K2), two integrin adaptors that promote metastasis, bind each other Binding of GIV or integrin to K2 allosterically enhances GIV•K2•integrin complexes Binding is required for the maximal recruitment of GIV and K2 to active integrins Binding facilitates integrin clustering, activation, tumor cell adhesion, invasion.

PDZ domains are one of the most abundant protein domains in eukaryotes and frequently found on junction-localized scaffold proteins. Various signaling molecules bind to PDZ proteins via PDZ-binding motifs (PBM) and finetune cellular signaling. Here we describe the presence of a PBM on GIV/Girdin (CCDC88A) that is conserved throughout evolution, from invertebrates to vertebrates, and is generated as a long isoform-variant in humans, which we named GIV-L . Unlike GIV, which lacks PBM and is cytosolic, GIV-L localizes to the cell junctions, and has a unique PDZ-interactome, which impacts GIV-L ’s ability to bind and activate trimeric G-protein, Gi through its g uanine-nucleotide e xchange m odulator (GEM) module; the GEM module is found exclusively in vertebrates. Thus, the two functional modules in GIV evolved sequentially: the ability to bind PDZ proteins via the PBM evolved earlier in invertebrates, whereas G-protein binding and activation may have evolved later only among vertebrates. Phenotypic studies in Caco-2 cells revealed that GIV and GIV-L may have antagonistic effects on cell growth, proliferation (cell cycle), and survival. Immunohistochemical analyses in human colon tissues showed that GIV expression increases with a concomitant decrease in GIV-L during cancer initiation. Taken together, these findings reveal how GIV/CCDC88A in humans displays evolutionary flexibility in modularity, which allows the resultant isoforms to play opposing roles either as a tumor suppressor (GIV-L) or as an oncogene (GIV).