Cytotoxin-associated-gene A (CagA) of Helicobacter pylori (H. pylori) is a virulence factor that plays critical roles in H. pylori-induced gastric inflammation. In the present study, gastric biopsies were used for genotyping cagA and vacA genes, determining the autophagic activity, and the severity of gastric inflammation response. It was revealed that autophagy in gastric mucosal tissues infected with cagA+ H. pylori strains was lower than the levels produced by cagA− H. pylori strains, accompanied with accumulation of SQSTM1 and decreased LAMP1 expression. In vitro, deletion mutant of cagA gene resulted in increased autophagic activity, and decreased expression of SQSTM1 and cytokines, whereas over-expression of CagA down-regulated the starvation-induced autophagy, and induced more production of the cytokines. Moreover, the production of the cytokines was increased by inhibition of autophagy, but decreased by enhancement of autophagy. Deletion of CagA decreased the ability to activate Akt kinase at Ser-473 site and increased autophagy. c-Met siRNA significantly affected CagA-mediated autophagy, and decreased the level of p-Akt, p-mTOR, and p-S6. Both c-Met siRNA and MK-2206 could reverse inflammatory response. H. pylori CagA protein negatively regulates autophagy and promotes the inflammation in H. pylori infection, which is regulated by c-Met-PI3K/Akt-mTOR signaling pathway activation.

Plants use seasonal temperature cues to time the transition to reproduction. In Arabidopsis thaliana, winter cold epigenetically silences the floral repressor locus FLOWERING LOCUS C (FLC) through POLYCOMB REPRESSIVE COMPLEX 2 (PRC2)1. This vernalization process aligns flowering with spring. A prerequisite for silencing is transcriptional downregulation of FLC, but how this occurs in the fluctuating temperature regimes of autumn is unknown2–4. Transcriptional repression correlates with decreased local levels of histone H3 trimethylation at K36 (H3K36me3) and H3 trimethylation at K4 (H3K4me3)5,6, which are deposited during FRIGIDA (FRI)-dependent activation of FLC7–10. Here we show that cold rapidly promotes the formation of FRI nuclear condensates that do not colocalize with an active FLC locus. This correlates with reduced FRI occupancy at the FLC promoter and FLC repression. Warm temperature spikes reverse this process, buffering FLC shutdown to prevent premature flowering. The accumulation of condensates in the cold is affected by specific co-transcriptional regulators and cold induction of a specific isoform of the antisense RNA COOLAIR5,11. Our work describes the dynamic partitioning of a transcriptional activator conferring plasticity in response to natural temperature fluctuations, thus enabling plants to effectively monitor seasonal progression.

Plants monitor many aspects of their fluctuating environments to help align their development with seasons. Molecular understanding of how noisy temperature cues are registered has emerged from dissection of vernalization in Arabidopsis, which involves a multiphase cold-dependent silencing of the floral repressor locus FLOWERING LOCUS C (FLC). Cold-induced transcriptional silencing precedes a low probability PRC2 epigenetic switching mechanism. The epigenetic switch requires the absence of warm temperatures as well as long-term cold exposure. However, the natural temperature inputs into the earlier transcriptional silencing phase are less well understood.Here, through investigation of Arabidopsis accessions in natural and climatically distinct field sites, we show that the first seasonal frost strongly induces expression of COOLAIR, the antisense transcripts at FLC. Chamber experiments delivering a constant mean temperature with different fluctuations showed the freezing induction of COOLAIR correlates with stronger repression of FLC mRNA. Identification of a mutant that ectopically activates COOLAIR revealed how COOLAIR up-regulation can directly reduce FLC expression. Consistent with this, transgenes designed to knockout COOLAIR perturbed the early phase of FLC silencing. However, all transgenes designed to remove COOLAIR resulted in increased production of novel convergent FLC antisense transcripts. Our study reveals how natural temperature fluctuations promote COOLAIR regulation of FLC, with the first autumn frost acting as a key indicator of autumn/winter arrival.