Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging. RNAi of the utx-1 gene extended the mean life span of C. elegans by ~30%, dependent on DAF-16 activity and not additive in daf-2 mutants. The loss of utx-1 increased H3K27me3 on the Igf1r/daf-2 gene and decreased IIS activity, leading to a more "naive" epigenetic state. Like stem cell reprogramming, our results suggest that reestablishment of epigenetic marks lost during aging might help "reset" the developmental age of animal cells.

A molecular‐scale gap array is introduced into a single‐layer graphene sheet by a lithographic dash‐line cutting process. Electrically active molecules are then covalently wired into these point contacts in high yield, thus forming stable molecular devices that for example are able to reversibly switch their conductance by chemical treatment.

The human genome contains approximately one million Alu repetitive elements comprising 10% of the genome, yet their functions are not well understood. Here, we show that Alu elements resemble enhancers. Alu elements are bound by two well-phased nucleosomes that contain histones bearing marks of active chromatin, and they show tissue-specific enrichment for the enhancer mark H3K4me1. A proportion of Alu elements were experimentally validated as bona fide active enhancers with an in vitro reporter assay. In addition, Hi-C data indicate that Alus show long-range interactions with gene promoters. We also find that Alus are generally more conserved when located in the proximal upstream region of genes. Their similarity to enhancers becomes more prominent with their age in the human genome, following a clear evolutionary continuum reminiscent of the evolutionary pattern of proto-genes. Therefore, we conclude that some Alu elements can function as enhancers and propose that many more may be proto-enhancers that serve as a repertoire for the de novo birth of enhancers.

Abnormalities in epigenetic modifiers are emerging as driving events in prostate cancer (PCa). The histone methyltransferase KMT2D, a frequently aberrant epigenetic modifier in various tumors, has an undefined role in PCa. Moreover, little is known regarding KMT2D’s mutation in Chinese patients or its downstream signaling pathways and targets. Here, we profiled the mutational spectrum of 32 significantly PCa-associated genes by using disease-targeted sequencing, and found that KMT2D was highly mutated (63.04%, 29/46) in Chinese patients. Moreover, high KMT2D transcription was also associated with poor prognosis in an independent cohort (n = 51). In KMT2D-knockdown PC-3 and DU145 cells, cell proliferation (P < 0.01), invasion (P < 0.001), and migration (P < 0.01) were consequently suppressed. KMT2D depletion effectively suppressed tumor growth by 92.21% in vivo. Notably, integrative analyses of RNAseq and ChIPseq characterized two crucial genes downregulated by KMT2D, leukemia inhibitory factor receptor (LIFR) and Kruppel-like factor-4 (KLF4), which are regulators in PI3K/Akt and EMT, respectively. Our present study revealed that KMT2D epigenetically activates PI3K/Akt pathway and EMT by targeting LIFR and KLF4 and thus serves as a putative epigenetic-based target for treating PCa.

BackgroundGrafting has been extensively used to enhance the performance of horticultural crops. Since Charles Darwin coined the term “graft hybrid” meaning that asexual combination of different plant species may generate products that are genetically distinct, highly discrepant opinions exist supporting or against the concept. Recent studies have documented that grafting enables exchanges of both RNA and DNA molecules between the grafting partners, thus providing a molecular basis for grafting-induced genetic variation. DNA methylation is known as prone to alterations as a result of perturbation of internal and external conditions. Given characteristics of grafting, it is interesting to test whether the process may cause an alteration of this epigenetic marker in the grafted organismal products.Methodology/Principal FindingsWe analyzed relative global DNA methylation levels and locus-specific methylation patterns by the MSAP marker and locus-specific bisulfite-sequencing in the seed plants (wild-type controls), self- and hetero-grafted scions/rootstocks, selfed progenies of scions and their seed-plant controls, involving three Solanaceae species. We quantified expression of putative genes involved in establishing and/or maintaining DNA methylation by q-(RT)-PCR. We found that (1) hetero-grafting caused extensive alteration of DNA methylation patterns in a locus-specific manner, especially in scions, although relative methylation levels remain largely unaltered; (2) the altered methylation patterns in the hetero-grafting-derived scions could be inherited to sexual progenies with some sites showing further alterations or revisions; (3) hetero-grafting caused dynamic changes in steady-state transcript abundance of genes encoding for a set of enzymes functionally relevant to DNA methylation.Conclusions/SignificanceOur results demonstrate that inter-species grafting in plants could produce extensive and heritable alterations in DNA methylation. We suggest that these readily altered, yet heritable, epigenetic modifications due to interspecies hetero-grafting may shed one facet of insight into the molecular underpinnings for the still contentious concept of graft hybrid.

Honey is a natural sweetener produced by honey bees from the secretions of plants. Honey is well-known for its nutritional and medicinal values since prehistoric times. In the present study, 40 honey samples were collected from supermarkets in China. These samples were produced in China and also imported from other countries. These samples were explored for the detection of 16 phenolic acids and 14 flavonoids by employing high-performance liquid chromatography (HPLC). Among the phenolic compounds explored, gallic acid (phenolic acid) and chrysin (flavonoid) were found to be the most dominant phenolic compounds. The phenolic profile of honey samples was greatly influenced by geographical location and floral sources. The classification of honey samples collected from various regions and floral sources (unifloral and multi-floral) were carried out using linear discriminant analysis (LDA) and it was observed that certain phenolic compounds significantly contributed towards the classification of honey samples collected from various geographical origin and floral source. Thus, this systematic study provides a fundamental knowledge of honey quality for therapeutic product development.

Edible flowers are referred to the non-toxic flowers that can be consumed by human beings for their additional nutritional or medical properties. These flowers are rich source of natural antioxidants, thus exert specific positive health effects on chronic diseases and act as a potential function food. This research paper is focused on the determination of total phenolic content (TPC), total flavonoids content (TFC), and antioxidant capacities of different kinds of edible flowers in China and compared systematically. Sixty-five flower samples were collected from parks in Guangzhou and also purchased from Qingping Market. TPC, TFC, and three anti-oxidative assays (DPPH free radical scavenging activity, ABTS radical scavenging activity, and Ferric reducing antioxidant capacity (FRAP) assay) were conducted. Different flowers presented diverse range of antioxidant capacities, phenolic contents, and flavonoid contents. A high correlation between TPC and antioxidant activity (as accessed using three different methods) was reported. However, a low relationship was observed between TFC value and antioxidant capacities. This study revealed that five Rosa species exhibited strong antioxidant capacities among other samples, and these can be used as potential functional foods to counterbalance the effect of reactive oxygen species (ROS) and oxidative stress. ARTICLE HISTORY

BackgroundThe study on phytochemical difference between red and black goji berry is limited.MethodsAntioxidant activities and phenolic profiles in terms of total phenol content, total flavonoid contents, condensed tannin content, monomeric anthocyanin content, and total carotenoid content of red goji berry (Lycium barbarum) and black goji berry (L. ruthenicum) were compared using colorimetric assays.ResultsAll goji berries were rich in phenolics. Black goji berry had the highest phenolic, condensed tannin content and monomeric anthocyanin content. Black goji berry samples possessed higher antioxidant capacities than red goji berry, while the red goji berry had the highest carotenoid content. Goji berries exhibited a positive linear correlation between phenolic compounds and antioxidant capacities. The average value of carotenoid content in red goji berry was 233.04 µg/g.ConclusionThe phenolics and antioxidant capacities are much higher in black goji berry than red goji berry, while carotenoid content is much higher in red than black.