a b s t r a c t CREB binding protein (CBP) is an acetyltransferase that plays an important role in many biological processes. Here, we show that Akt phosphorylates CBP at threonine 1871 and suppresses its acetyltransferase activity by impeding the binding of CBP to histone H3, which results in a decrease in lysine K18 acetylation and dysregulation of target genes. Our results demonstrate that Akt regulates acetyltransferase activity through CBP phosphorylation, which may contribute to tumorigenesis. Structured summary of protein interactions:CBP physically interacts with AKT1 by anti tag coimmunoprecipitation (View Interaction: 1, 2) CBP physically interacts with AKT1 by anti tag coimmunoprecipitation (View interaction)
Lithocarpus polystachyus Rehd. is an important medicinal plant species grown in southern China, with phlorizin as its main active substance. The effects of light conditions on phlorizin biosynthesis in L. polystachyus remain unclear. Thus, we analyzed the transcriptomes of L. polystachyus plants cultivated under diverse light qualities, light intensities, and photoperiods. The light treatments resulted in 5977–8027 differentially expressed genes (DEGs), which were functionally annotated based on the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Genes encoding transcription factors from 89 families were differentially expressed after the light treatments, implying these transcription factors are photoresponsive. Phenylalanine ammonia lyase (PAL) and 4-coumarate-CoA ligase (4CL) are the key enzymes for the accumulation of phlorizin. The transcription levels of PAL2, PAL, 4CL1 (DN121614), 4CLL7, and 4CL1 (DN102161) were positively correlated with phlorizin accumulation, suggesting that these genes are important for phlorizin biosynthesis. An ultra-high-performance liquid chromatography method was used to quantify the phlorizin content. Phlorizin accumulated in response to the green light treatment and following appropriate decreases in the light intensity or appropriate increases in the duration of the light exposure. The green light, 2000 lx, and 3000 lx treatments increased the PAL activity of L. polystachyus, but the regulatory effects of the light intensity treatments on PAL activity were relatively weak. This study represents the first comprehensive analysis of the light-induced transcriptome of L. polystachyus. The study results may form the basis of future studies aimed at elucidating the molecular mechanism underlying phlorizin biosynthesis in L. polystachyus. Moreover, this study may be relevant for clarifying the regulatory effects of light on the abundance of bioactive components in medicinal plants.
The WRKY transcription factors family, which participates in many physiological processes in plants, constitutes one of the largest transcription factor families. The Asterales and the Apiales are two orders of flowering plants in the superorder Asteranae. Among the members of the Asterales, globe artichoke (Cynara cardunculus var. scolymus L.), sunflower (Helianthus annuus L.), and lettuce (Lactuca sativa L.) are important economic crops worldwide. Within the Apiales, ginseng (Panax ginseng C. A. Meyer) and Panax notoginseng (Burk.) F.H. Chen are important medicinal plants, while carrot (Daucus carota subsp. carota L.) has significant economic value. Research involving genome-wide identification of WRKY transcription factors in the Asterales and the Apiales has been limited. In this study, 490 WRKY genes, 244 from three species of the Apiales and 246 from three species of the Asterales, were identified and categorized into three groups. Within each group, WRKY motif characteristics and gene structures were similar. WRKY gene promoter sequences contained light responsive elements, core regulatory elements, and 12 abiotic stress cis-acting elements. WRKY genes were evenly distributed on each chromosome. Evidence of segmental and tandem duplication events was found in all six species in the Asterales and the Apiales, with segmental duplication inferred to play a major role in WRKY gene evolution. Among the six species, we uncovered 54 syntenic gene pairs between globe artichoke and lettuce. The six species are thus relatively closely related, consistent with their traditional taxonomic placement in the Asterales. This study, based on traditional species classifications, was the first to identify WRKY transcription factors in six species from the Asteranae. Our results lay a foundation for further understanding of the role of WRKY transcription factors in species evolution and functional differentiation.
Eleutherococcus senticosus (Ruper. et Maxim.) Maxim is a traditional Chinese medicine. The saponin components of E. senticosus have several biological effects, including reduction of blood lipids; protection against liver, heart, and vascular disease; and antitumor activity. The DNA methylation of E. senticosus farnesyl pyrophosphate synthase (FPS), squalene synthase (SS), and squalene epoxidase (SE) gene promoters and the mechanism of the influence of these enzymes on saponin synthesis and accumulation in E. senticosus were explored using bisulfite sequencing technology, real-time PCR, the vanillin-concentrated sulfuric acid chromogenic method, and LC-MS. There are 19 DNA methylation sites and 8 methylation types in the FPS gene. The SS gene has nine DNA methylation sites and two DNA methylation types. The SE gene has 16 DNA methylation sites and 7 methylation types. The total saponin content in the high and low DNA methylation groups were 1.07 ± 0.12 and 2.92 ± 0.32 mg/g, respectively. Statistical analysis indicated that the gene expression of the FPS, SS, and SE genes was significantly positively correlated with the saponin content (p < 0.05), and that the methylation ratio was significantly negatively correlated with the saponin content (p < 0.01), while the expression of the SS and SE genes was significantly positively correlated (p < 0.01). A total of 488 metabolites were detected from E. senticosus and 100 different metabolites were screened out by extensive targeted metabolomics. The amount of most metabolites related to the mevalonate pathway was higher in the low DNA methylation group than in the high DNA methylation group. It was demonstrated that there are DNA methylation sites in the promoter regions of the FPS, SS, and SE genes of E. senticosus, and DNA methylation in this region could significantly inhibit synthesis in the mevalonate pathway, thus reducing the content of the final product E. senticosus saponin.
The proto-oncogene c-Jun plays essential roles in various cellular processes, including cell proliferation, cell differentiation, and cellular apoptosis. Enormous efforts have been made to understand the mechanisms regulating c-Jun activation. The males absent on the first (MOF)-containing non-specific lethal (NSL) complex has been shown to positively regulate gene expression. However, the biological function of the NSL complex is largely unknown. Here we present evidence showing that c-Jun recruits the NSL complex to c-Jun target genes upon activation. The NSL complex catalyzes H4K16 acetylation at c-Jun target genes, thereby promoting c-Jun target gene transcription. More interestingly, we also found that the NSL complex promotes the release of the repressive NuRD complex from c-Jun target genes, thus activating c-Jun. Our findings not only reveal a new mechanism regulating c-Jun activation, but also identify the NSL complex as a c-Jun co-activator in c-Jun-regulated gene expression, expanding our knowledge of the function of the NSL complex in gene expression regulation.
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