36 research outputs found

    Maternal Wnt/ÎČ-Catenin Signaling Coactivates Transcription through NF-ÎșB Binding Sites during Xenopus Axis Formation

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    Maternal Wnt/ÎČ-Catenin signaling establishes a program of dorsal-specific gene expression required for axial patterning in Xenopus. We previously reported that a subset of dorsally expressed genes depends not only on Wnt/ÎČ-Catenin stimulation, but also on a MyD88-dependent Toll-like receptor/IL1-receptor (TLR/IL1-R) signaling pathway. Here we show that these two signal transduction cascades converge in the nucleus to coactivate gene transcription in blastulae through a direct interaction between ÎČ-Catenin and NF-ÎșB proteins. A transdominant inhibitor of NF-ÎșB, ΔNIÎșBα, phenocopies loss of MyD88 protein function, implicating Rel/NF-ÎșB proteins as selective activators of dorsal-specific gene expression. Sensitive axis formation assays in the embryo demonstrate that dorsalization by Wnt/ÎČ-Catenin requires NF-ÎșB protein activity, and vice versa. Xenopus nodal-related 3 (Xnr3) is one of the genes with dual ÎČ-Catenin/NF-ÎșB input, and a proximal NF-ÎșB consensus site contributes to the regional activity of its promoter. We demonstrate in vitro binding of Xenopus ÎČ-Catenin to several XRel proteins. This interaction is observed in vivo upon Wnt-stimulation. Finally, we show that a synthetic luciferase reporter gene responds to both endogenous and exogenous ÎČ-Catenin levels in an NF-ÎșB motif dependent manner. These results suggest that ÎČ-Catenin acts as a transcriptional co-activator of NF-ÎșB-dependent transcription in frog primary embryonic cells

    GH and the cardiovascular system: an update on a topic at heart

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    Mapping circulating serum miRNAs to their immune-related target mRNAs

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    Bakhtiyor Nosirov,1 Joël Billaud,1 Alexis Vandenbon,2 Diego Diez,3 Edward Wijaya,1 Ken J Ishii,4,5 Shunsuke Teraguchi,3 Daron M Standley1,6 1Systems Immunology Lab, 2Immuno-Genomics Research Unit, 3Quantitative Immunology Research Unit, 4Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Suita, 5Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Osaka, 6Lab of Integrated Biological Information, Institute for Virus Research Kyoto University, Kyoto, Japan Purpose: Evidence suggests that circulating serum microRNAs (miRNAs) might preferentially target immune-related mRNAs. If this were the case, we hypothesized that immune-related mRNAs would have more predicted serum miRNA binding sites than other mRNAs and, reciprocally, that serum miRNAs would have more immune-related mRNA targets than non-serum miRNAs.Materials and methods: We developed a consensus target predictor using the random forest framework and calculated the number of predicted miRNA–mRNA interactions in various subsets of miRNAs (serum, non-serum) and mRNAs (immune related, nonimmune related).Results: Immune-related mRNAs were predicted to be targeted by serum miRNA more than other mRNAs. Moreover, serum miRNAs were predicted to target many more immune-related mRNA targets than non-serum miRNAs; however, these two biases in immune-related mRNAs and serum miRNAs appear to be completely independent.Conclusion: Immune-related mRNAs have more miRNA binding sites in general, not just for serum miRNAs; likewise, serum miRNAs target many more mRNAs than non-serum miRNAs overall, regardless of whether they are immune related or not. Nevertheless, these two independent phenomena result in a significantly larger number of predicted serum miRNA–immune mRNA interactions than would be expected by chance. Keywords: biomarker, posttranscriptional regulation, random forest, target predictio

    Interspecific variation across angiosperms in global DNA methylation: phylogeny, ecology and plant features in tropical and Mediterranean communities

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    The interspecific range of epigenetic variation and the degree to which differences between angiosperm species are related to geography, evolutionary history, ecological settings or species-specific traits, remain essentially unexplored. Genome-wide global DNA cytosine methylation is a tractable ‘epiphenotypic’ feature suitable for exploring these relationships. Global cytosine methylation was estimated in 279 species from two distant, ecologically disparate geographical regions: Mediterranean Spain and tropical MĂ©xico. At each region, four distinct plant communities were analyzed. Global methylation spanned a 10-fold range among species (4.8–42.2%). Interspecific differences were related to evolutionary trajectories, as denoted by a strong phylogenetic signal. Genomes of tropical species were on average less methylated than those of Mediterranean ones. Woody plants have genomes with lower methylation than perennial herbs, and genomes of widespread species were less methylated than those of species with restricted geographical distribution. The eight communities studied exhibited broad and overlapping interspecific variances in global cytosine methylation and only two of them differed in average methylation. Altogether, our broad taxonomic survey supported global methylation as a plant ‘epiphenotypic’ trait largely associated with species evolutionary history, genome size, range size and woodiness. Additional studies are required for better understanding the environmental components underlying local and geographical variation.Peer Reviewe
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