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The recent growth in the number of publicly available cancer omics databases has been accompanied by the development of various tools that allow researchers to visually explore these data. In 2015, we built MEXPRESS, an online tool for the integration and visualization of gene expression, DNA methylation and clinical data from The Cancer Genome Atlas (TCGA), a large collection of publicly available multi-omics cancer data. MEXPRESS addresses the need for an easy-to-use, interactive application that allows researchers to identify dysregulated genes and their clinical relevance in cancer. Furthermore, while other tools typically do not support integrated visualization of expression and DNA methylation data in combination with the precise genomic location of the methylation, MEXPRESS is unique in how it depicts these diverse data types together. Motivated by the large number of users MEXPRESS has managed to attract over the past 3 years and the recent migration of all TCGA data to a new data portal, we developed a new version of MEXPRESS (https://mexpress.be). It contains the latest TCGA data, additional types of omics and clinical data and extra functionality, allowing users to explore mechanisms of gene dysregulation beyond expression and DNA methylation., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Ribosome-inactivating proteins (RIPs) are plant enzymes that target the rRNA. The cytoplasmic RIP, called OsRIP1, plays a crucial role in regulating jasmonate, a key plant hormone. Understanding the role of OsRIP1 can provide insights into enhancing stress tolerance and optimizing growth of rice. Transcription profiling by mRNA sequencing was employed to measure the changes in gene expression in rice plants in response to MeJA treatment. Compared to wild type (WT) plants, OsRIP1 overexpressing rice plants showed a lower increase in mRNA transcripts for genes related to jasmonate responses when exposed to MeJA treatment for 3 h. After 24 h of MeJA exposure, the mRNA transcripts associated with the gibberellin pathway occurred in lower levels in OsRIP1 overexpressing plants compared to WT plants. We hypothesize that the mechanism underlying OsRIP1 antagonization of MeJA-induced shoot growth inhibition involves cytokininmediated leaf senescence and positive regulation of cell cycle processes, probably via OsRIP1 interaction with 40S ribosomal protein S5 and α-tubulin. Moreover, the photosystem II 10kDa polypeptide was identified to favorably bind to OsRIP1, and its involvement may be attributed to the reduction of photosynthesis in OsRIP1-overexpressing plants subjected to MeJA at the early timepoint (3 h). [ABSTRACT FROM AUTHOR]

Background: Hibernation (torpor) is a strategy to survive extreme environmental conditions, associated with a significant decrease in metabolism and body temperature. The inducibility by the environment of torpor for facultative hibernators designates epigenetic mechanisms as likely candidates for regulation. Therefore, we set out to unravel epigenetics in the liver of a facultative hibernator, Syrian hamster (Mesocricetus auratus), sampled at different phases during hibernation, by assessing the expression of epigenetic writer and eraser enzymes, histone acetylation dynamics, and DNA methylation levels. Results: Expression of epigenetic writers/erasers confirmed previously reported results obtained in obligatory hibernators, but might point to a mechanism specific for facultative hibernators, e.g., differential expression of histone acetyltransferases (HATs; KAT6A, KAT6B, KAT7, and KAT13D/CLOCK). These findings were in accordance with observed changes in histone H3 and H4 acetylation changes. Overall histone deacetylase (HDAC) activity was highest in torpor. No differences were detected in DNA methylation throughout all phases. Conclusion: Our study thus points to histone acetylation as an important player in facultative hamster hibernation, which may underlie the orchestration of gene expression changes throughout hibernation. [ABSTRACT FROM AUTHOR]

Background: DNA hypermethylation is an epigenetic feature that modulates gene expression, and its deregulation is observed in cancer. Previously, we identified a neural-related DNA hypermethylation fingerprint in colon cancer, where most of the top hypermethylated and downregulated genes have known functions in the nervous system. To evaluate the presence of this signature and its relevance to carcinogenesis in general, we considered 16 solid cancer types available in The Cancer Genome Atlas (TCGA). Results: All tested cancers showed significant enrichment for neural-related genes amongst hypermethylated genes. This signature was already present in two premalignant tissue types and could not be explained by potential confounders such as bivalency status or tumor purity. Further characterization of the neural-related DNA hypermethylation signature in colon cancer showed particular enrichment for genes that are overexpressed during neural differentiation. Lastly, an analysis of upstream regulators identified RE1-Silencing Transcription factor (REST) as a potential mediator of this DNA methylation signature. Conclusion: Our study confirms the presence of a neural-related DNA hypermethylation fingerprint in various cancers, of genes linked to neural differentiation, and points to REST as a possible regulator of this mechanism. We propose that this fingerprint indicates an involvement of DNA hypermethylation in the preservation of neural stemness in cancer cells. [ABSTRACT FROM AUTHOR]

Hibernation consists of alternating torpor–arousal phases, during which animals cope with repetitive hypothermia and ischaemia-reperfusion. Due to limited transcriptomic and methylomic information for facultative hibernators, we here conducted RNA and whole-genome bisulfide sequencing in liver of hibernating Syrian hamster (Mesocricetus auratus). Gene ontology analysis was performed on 844 differentially expressed genes and confirmed the shift in metabolic fuel utilization, inhibition of RNA transcription and cell cycle regulation as found in seasonal hibernators. Additionally, we showed a so far unreported suppression of mitogen-activated protein kinase (MAPK) and protein phosphatase 1 pathways during torpor. Notably, hibernating hamsters showed upregulation of MAPK inhibitors (dual-specificity phosphatases and sproutys) and reduced levels of MAPK-induced transcription factors (TFs). Promoter methylation was found to modulate the expression of genes targeted by these TFs. In conclusion, we document gene regulation between hibernation phases, which may aid the identification of pathways and targets to prevent organ damage in transplantation or ischaemia-reperfusion. [ABSTRACT FROM AUTHOR]

The extreme adaptation potential of the generalist herbivore Tetranychus urticae (the two-spotted spider mite) to pesticides as well as diverse host plants has been associated with clade-specific gene expansions in known detoxifying enzyme families, and with extensive and rapid transcriptional responses. However, how this broad transcriptional potential is regulated remains largely unknown. Using a parental/F1 design in which four inbred strains were crossed to a common inbred strain, we assessed the genetic basis and inheritance of gene expression variation in T. urticae. Mirroring known phenotypic variation in the progenitor strains of the inbreds, we confirmed that the inbred strains we created were genetically distinct, varied markedly in pesticide resistance, and also captured variation in host plant fitness as is commonly observed in this species. By examining differences in gene expression between parents and allele-specific expression in F1s, we found that variation in RNA abundance was more often explained in trans as compared to cis, with the former associated with dominance in inheritance. Strikingly, in a gene ontology analysis, detoxification genes of the cytochrome P450 monooxygenase (CYP) family, as well as dioxygenases (DOGs) acquired from horizontal gene transfer from fungi, were specifically enriched at the extremes of trans-driven up- and downregulation. In particular, multiple CYPs and DOGs with broad substrate-specificities for pesticides or plant specialized compounds were exceptionally highly upregulated as a result of trans-regulatory variation, or in some cases synergism of cis and trans, in the most multi-pesticide resistant strains. Collectively, our findings highlight the potential importance of trans-driven expression variation in genes associated with xenobiotic metabolism and host plant use for rapid adaptation in T. urticae, and also suggests modular control of these genes, a regulatory architecture that might ameliorate negative pleiotropic effects. Author summary: The two-spotted spider mite, Tetranychus urticae, is a generalist herbivore and pest of diverse crops globally. In response to the plethora of chemicals used for its control, the species rapidly evolves pesticide resistance. Further, experimental evolution studies with T. urticae populations have demonstrated adaptation to challenging host plants in as few as five generations. The adaptation of T. urticae to pesticides and host plants has been associated with large transcriptome changes, including for genes associated with detoxification of pesticides and toxic plant compounds. Nevertheless, the basis of the observed transcriptome variation has remained largely unknown. Here, we examined the genetic control and inheritance of expression differences among five inbred T. urticae strains, including several with histories of intense pesticide selection. With a parental/F1 experimental design, we found that trans effects were common in explaining variation in detoxification gene expression, with the trans-driven upregulation of a subset of cytochrome P450 monooxygenases of broad substrate specificity especially striking in the most pesticide resistant strains. Our findings suggest that genetic variation acting with dominant or additive inheritance to impact the regulation of modules of detoxification genes may be an important target of selection during rapid pesticide and host plant evolution in herbivores. [ABSTRACT FROM AUTHOR]

Background: Brine shrimp Artemia have an unequalled ability to endure extreme salinity and complete anoxia. This study aims to elucidate its strategies to cope with these stressors. Results and discussion: Here, we present the genome of an inbred A. franciscana Kellogg, 1906. We identified 21,828 genes of which, under high salinity, 674 genes and under anoxia, 900 genes were differentially expressed (42%, respectively 30% were annotated). Under high salinity, relevant stress genes and pathways included several Heat Shock Protein and Leaf Embryogenesis Abundant genes, as well as the trehalose metabolism. In addition, based on differential gene expression analysis, it can be hypothesized that a high oxidative stress response and endocytosis/exocytosis are potential salt management strategies, in addition to the expression of major facilitator superfamily genes responsible for transmembrane ion transport. Under anoxia, genes involved in mitochondrial function, mTOR signalling and autophagy were differentially expressed. Both high salt and anoxia enhanced degradation of erroneous proteins and protein chaperoning. Compared with other branchiopod genomes, Artemia had 0.03% contracted and 6% expanded orthogroups, in which 14% of the genes were differentially expressed under high salinity or anoxia. One phospholipase D gene family, shown to be important in plant stress response, was uniquely present in both extremophiles Artemia and the tardigrade Hypsibius dujardini, yet not differentially expressed under the described experimental conditions. Conclusions: A relatively complete genome of Artemia was assembled, annotated and analysed, facilitating research on its extremophile features, and providing a reference sequence for crustacean research. [ABSTRACT FROM AUTHOR]

Epigenetic processes play a crucial role in the regulation of plant stress responses, but their role in plant–pathogen interactions remains poorly understood. Although histone‐modifying enzymes have been observed to be deregulated in galls induced by root‐knot nematodes (RKN, Meloidogyne graminicola) in rice, their influence on plant defence and their genome‐wide impact has not been comprehensively investigated. First, the role of histone modifications in plant–nematode interactions was confirmed by pharmacological inhibition of histone‐modifying enzymes, which all significantly affected rice susceptibility to RKN. For a more specific view, three histone marks, H3K9ac, H3K9me2, and H3K27me3, were subsequently studied by chromatin‐immunoprecipitation‐sequencing on RKN‐induced galls at 3 days postinoculation. While levels of H3K9ac and H3K27me3 were strongly enriched, H3K9me2 was generally depleted in galls versus control root tips. Differential histone peaks were generally associated with plant defence‐related genes. Transcriptome analysis using RNA‐Seq and RT‐qPCR‐based validation revealed that genes marked with H3K9ac or H3K9me2 showed the expected activation or repression gene expression pattern, but this was not the case for H3K27me3 marks. Our results indicate that histone modifications respond dynamically to RKN infection, and that posttranslational modifications mainly at H3K9 specifically target plant defence‐related genes. [ABSTRACT FROM AUTHOR]

DNA-methylation is an important epigenetic feature in health and disease. Methylated sequence capturing by Methyl Binding Domain (MBD) based enrichment followed by second-generation sequencing provides the best combination of sensitivity and cost-efficiency for genome-wide DNA-methylation profiling. However, existing implementations are numerous, and quality control and optimization require expensive external validation. Therefore, this study has two aims: 1) to identify a best performing kit for MBD-based enrichment using independent validation data, and 2) to evaluate whether quality evaluation can also be performed solely based on the characteristics of the generated sequences. Five commercially available kits for MBD enrichment were combined with Illumina GAIIx sequencing for three cell lines (HCT15, DU145, PC3). Reduced representation bisulfite sequencing data (all three cell lines) and publicly available Illumina Infinium BeadChip data (DU145 and PC3) were used for benchmarking. Consistent large-scale differences in yield, sensitivity and specificity between the different kits could be identified, with Diagenode's MethylCap kit as overall best performing kit under the tested conditions. This kit could also be identified with the Fragment CpG-plot, which summarizes the CpG content of the captured fragments, implying that the latter can be used as a tool to monitor data quality. In conclusion, there are major quality differences between kits for MBD-based capturing of methylated DNA, with the MethylCap kit performing best under the used settings. The Fragment CpG-plot is able to monitor data quality based on inherent sequence data characteristics, and is therefore a cost-efficient tool for experimental optimization, but also to monitor quality throughout routine applications. [ABSTRACT FROM AUTHOR]

Abstract: Several lines of evidence have linked limb teratogenesis to radiation-induced apoptosis and to the p53 status in murine fetuses. In previous reports, we studied the occurrence of various malformations after intrauterine irradiation and showed that these malformations were modulated by p53-deficiency as well as by the developmental stage at which embryos were irradiated. In this new study, we focused onto one particular phenotype namely forelimb defects to further unravel the cellular and molecular mechanisms underlying this malformation. We measured various parameters expected to be directly or indirectly influenced by irradiation damage. The mouse fetuses were irradiated at day 12 p.c. (post conception) and examined for forelimb defects on gestational days 15, 16, 17 and 19 of development. The release of inflammatory cytokines was determined in the amniotic fluid on day 16 p.c. and the mean telomere lengths assessed at days 12, 13 and 19 p.c. Differential gene expression within the forelimb bud tissues was determined using Real Time quantitative PCR (RTqPCR) 24 h following irradiation. Apoptosis was investigated in the normal and malformed fetuses using the TUNEL assay and RTqPCR. First, we found that irradiated fetuses with forelimb defects displayed excessive apoptosis in the predigital regions. Besides, overexpression of the pro-apoptotic Bax gene indicates a mitochondrial-mediated cell death. Secondly, our results showed overexpression of MKK3 and MKK7 (members of the stress-activated MAP kinase family) within the malformed fetuses. The latter could be involved in radiation-induced apoptosis through activation of the p38 and JNK pathways. Thirdly, we found that irradiated fetuses exhibiting forelimb defects showed a marked telomere shortening. Interestingly, telomere shortening was observed as the malformations became apparent. Fourthly, we measured cytokine levels in the amniotic fluid and detected a considerable inflammatory reaction among the irradiated fetuses as evidenced by the increase in pro-inflammatory cytokine levels. Altogether, our data suggest that transcriptional modulations of apoptotic, inflammation, stress, and DNA damage players are early events in radiation-induced forelimb defects. These changes resulted in harsh developmental conditions as indicated by a marked increase in cytokine levels in the amniotic fluid and telomere shortening, two features concomitant with the onset of the forelimb defect phenotype in our study. [Copyright &y& Elsevier]