23 results on '"Denil S"'
Search Results
2. 526 Targeted sequencing of filaggrin identifies novel loss-of-function mutations in pediatric African American patients with severe atopic dermatitis
- Author
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Mathyer, M., primary, Quiggle, A., additional, Bayliss, S., additional, Wong, C., additional, Denil, S., additional, Common, J., additional, and de Guzman Strong, C., additional
- Published
- 2017
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- View/download PDF
3. 533 Array-based sequencing of filaggrin gene for comprehensive detection of disease-associated variants
- Author
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Wong, C., primary, Denil, S., additional, Foo, J., additional, Chen, H., additional, Tay, A., additional, Haines, R., additional, Tang, M., additional, McLean, I., additional, Lane, B., additional, Liu, J., additional, and Common, J., additional
- Published
- 2017
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- View/download PDF
4. The role of methylation in metastasis of oral squamous cell carcinoma: Understanding the OSCC methylome
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Clausen, M., Melchers, L.J., De Meyer, T., Denil, S., Criekinge, W., Wisman, G.B., Roodenburg, J.L.N., Schuuring, E., Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
diagnosis ,survival ,primary tumor ,promoter region ,data base ,chromosome 7 ,metastasis ,human ,hospital ,gene ,genome ,mouth squamous cell carcinoma ,metastasis potential ,marker ,therapy ,DNA methylation ,epigenetics ,lymph node metastasis ,messenger RNA ,imaging ,DNA ,lymph node ,biological marker ,stomatognathic diseases ,quality of life ,palpation ,methylation ,patient ,neoplasm - Abstract
Background: Oral Squamous Cell Carcinoma (OSCC) is characterized by an increasing incidence and a 60% 5-year survival. The most important prognostic factor for OSCC is the presence of lymph node (LN) metastases but the detection of LN metastases in the clinic by palpation and imaging is inaccurate resulting in under and overtreatment of patients. To improve LN diagnosis new detection methods are needed. DNA methylation studies can be used to identify novel biomarkers, as epigenetics have been established as an important regulator of metastatic potential. The aim of this study is to identify new DNA methylation markers that predict LN metastasis in OSCC. Materials and Methods: Genome-wide methylation patterns of metastatic (n = 6) and non-metastatic OSCC (n = 6) were assessed using MethylCap- Seq. Subsequently, analysis was performed on the most differentially methylated loci to identify pathways and genomic loci associated with LN metastasis. Additionally, the methylation data were combined with expression data of 222 OSCC patients acquired by an expression microarray with a 696 gene panel associated with N-status in OSCC. Finally, we validated these findings on the OSCC samples (n = 174) in The Cancer Genome Atlas (TCGA). Results: We found that genes on chromosome 7 are the most hypermethylated in metastatic OSCC in comparison to non-metastatic OSCC, more specifically a four million bp loci around the EGFR gene. In total 26 genes were found to be differentially methylated by MethylCap- Seq as well as differentially expressed by microarray. In the OSCC TCGA validation cohort, all 26 genes are significantly differentially expressed between metastatic and non-metastatic OSCC. For these 26 differentially expressed genes 88 probes were found in the TCGA Infinium 450k methylation data that are both significantly differentially methylated between the two groups and correlated with mRNA levels. Finally, six of these probes overlapped with the genomic regions annotated by MethylCap-Seq, representing five genes. Conclusion: We identified chromosomal loci, pathways and gene promoters associated with LN metastasis in OSCC patients. For 10 genes the differential methylation, expression and correlation between methylation and expression was validated on an independent OSCC cohort from the TCGA database. Increased understanding of the metastatic OSCC methylome will contribute to the identification of DNA methylation markers, pathways and potential therapeutic targets in OSCC primary tumors that will improve chances of providing the proper lymph node treatment and may result in improvement of survival and quality of life.
- Published
- 2014
5. RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis
- Author
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Clausen, M. J. A. M., primary, Melchers, L. J., additional, Mastik, M. F., additional, Slagter-Menkema, L., additional, Groen, H. J. M., additional, Laan, B. F. A. M. van der, additional, van Criekinge, W., additional, de Meyer, T., additional, Denil, S., additional, van der Vegt, B., additional, Wisman, G. B. A., additional, Roodenburg, J. L. N., additional, and Schuuring, E., additional
- Published
- 2016
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6. Discovery of new methylation markers to improve screening for cervical intraepithelial neoplasia grade 2/3
- Author
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Boers, A., primary, Wang, R., additional, van Leeuwen, R. W., additional, Klip, H. G., additional, de Bock, G. H., additional, Hollema, H., additional, van Criekinge, W., additional, de Meyer, T., additional, Denil, S., additional, van der Zee, A. G J., additional, Schuuring, E., additional, and Wisman, G. B. A., additional
- Published
- 2016
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7. 441 The role of méthylation in metastasis of oral squamous cell carcinoma: understanding the OSCC methylome
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Clausen, M., primary, Melchers, L.J., additional, de Meyer, T., additional, Denil, S., additional, Criekinge, W., additional, Wisman, G.B., additional, Roodenburg, J.L.N., additional, and Schuuring, E., additional
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- 2014
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8. Transcriptome analysis of rice mature root tissue and root tips in early development by massive parallel sequencing
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Kyndt, T., primary, Denil, S., additional, Haegeman, A., additional, Trooskens, G., additional, De Meyer, T., additional, Van Criekinge, W., additional, and Gheysen, G., additional
- Published
- 2012
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9. Nanopore Sequencing Enables Allelic Phasing of FLG Loss-of-Function Variants, Intragenic Copy Number Variation, and Methylation Status in Atopic Dermatitis and Ichthyosis Vulgaris.
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Wong C, Tham CY, Yang L, Benton MC, Narang V, Denil S, Duan K, Yew YW, Lee B, Florez de Sessions P, and Common JEA
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- Humans, Loss of Function Mutation, Intermediate Filament Proteins genetics, Female, Male, Filaggrin Proteins, Dermatitis, Atopic genetics, Ichthyosis Vulgaris genetics, DNA Copy Number Variations, DNA Methylation, Alleles
- Published
- 2024
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10. H3K4me3 remodeling induced acquired resistance through O-GlcNAc transferase.
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Ravindran Menon D, Hammerlindl H, Gimenez G, Hammerlindl S, Zuegner E, Torrano J, Bordag N, Emran AA, Giam M, Denil S, Pavelka N, Tan AC, Sturm RA, Haass NK, Rancati G, Herlyn M, Magnes C, Eccles MR, Fujita M, and Schaider H
- Subjects
- Humans, Down-Regulation, Mixed Function Oxygenases, Proto-Oncogene Proteins, Histones genetics, AMP-Activated Protein Kinases
- Abstract
Aims: Drivers of the drug tolerant proliferative persister (DTPP) state have not been well investigated. Histone H3 lysine-4 trimethylation (H3K4me3), an active histone mark, might enable slow cycling drug tolerant persisters (DTP) to regain proliferative capacity. This study aimed to determine H3K4me3 transcriptionally active sites identifying a key regulator of DTPPs., Methods: Deploying a model of adaptive cancer drug tolerance, H3K4me3 ChIP-Seq data of DTPPs guided identification of top transcription factor binding motifs. These suggested involvement of O-linked N-acetylglucosamine transferase (OGT), which was confirmed by metabolomics analysis and biochemical assays. OGT impact on DTPPs and adaptive resistance was explored in vitro and in vivo., Results: H3K4me3 remodeling was widespread in CPG island regions and DNA binding motifs associated with O-GlcNAc marked chromatin. Accordingly, we observed an upregulation of OGT, O-GlcNAc and its binding partner TET1 in chronically treated cancer cells. Inhibition of OGT led to loss of H3K4me3 and downregulation of genes contributing to drug resistance. Genetic ablation of OGT prevented acquired drug resistance in in vivo models. Upstream of OGT, we identified AMPK as an actionable target. AMPK activation by acetyl salicylic acid downregulated OGT with similar effects on delaying acquired resistance., Conclusion: Our findings uncover a fundamental mechanism of adaptive drug resistance that governs cancer cell reprogramming towards acquired drug resistance, a process that can be exploited to improve response duration and patient outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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11. Metabolic pathway analyses identify proline biosynthesis pathway as a promoter of liver tumorigenesis.
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Ding Z, Ericksen RE, Escande-Beillard N, Lee QY, Loh A, Denil S, Steckel M, Haegebarth A, Wai Ho TS, Chow P, Toh HC, Reversade B, Gruenewald S, and Han W
- Subjects
- Aldehyde Dehydrogenase deficiency, Aldehyde Dehydrogenase genetics, Animals, Carcinogenesis genetics, Carcinoma, Hepatocellular chemically induced, Carcinoma, Hepatocellular pathology, Cell Proliferation genetics, Diethylnitrosamine adverse effects, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, HEK293 Cells, HaCaT Cells, Hep G2 Cells, Humans, Liver Neoplasms chemically induced, Liver Neoplasms pathology, Liver Neoplasms, Experimental genetics, Liver Neoplasms, Experimental pathology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Nude, Mice, SCID, Pyrroline Carboxylate Reductases deficiency, Pyrroline Carboxylate Reductases genetics, Rats, Transcriptome, Transfection, Tumor Burden genetics, Xenograft Model Antitumor Assays, delta-1-Pyrroline-5-Carboxylate Reductase, Carcinogenesis metabolism, Carcinoma, Hepatocellular metabolism, Liver Neoplasms metabolism, Liver Neoplasms, Experimental metabolism, Proline biosynthesis, Signal Transduction genetics
- Abstract
Background & Aim: Under the regulation of various oncogenic pathways, cancer cells undergo adaptive metabolic programming to maintain specific metabolic states that support their uncontrolled proliferation. As it has been difficult to directly and effectively inhibit oncogenic signaling cascades with pharmaceutical compounds, focusing on the downstream metabolic pathways that enable indefinite growth may provide therapeutic opportunities. Thus, we sought to characterize metabolic changes in hepatocellular carcinoma (HCC) development and identify metabolic targets required for tumorigenesis., Methods: We compared gene expression profiles of Morris Hepatoma (MH3924a) and DEN (diethylnitrosamine)-induced HCC models to those of liver tissues from normal and rapidly regenerating liver models, and performed gain- and loss-of-function studies of the identified gene targets for their roles in cancer cell proliferation in vitro and in vivo., Results: The proline biosynthetic enzyme PYCR1 (pyrroline-5-carboxylate reductase 1) was identified as one of the most upregulated genes in the HCC models. Knockdown of PYCR1 potently reduced cell proliferation of multiple HCC cell lines in vitro and tumor growth in vivo. Conversely, overexpression of PYCR1 enhanced the proliferation of the HCC cell lines. Importantly, PYCR1 expression was not elevated in the regenerating liver, and KD or overexpression of PYCR1 had no effect on proliferation of non-cancerous cells. Besides PYCR1, we found that additional proline biosynthetic enzymes, such as ALDH18A1, were upregulated in HCC models and also regulated HCC cell proliferation. Clinical data demonstrated that PYCR1 expression was increased in HCC, correlated with tumor grade, and was an independent predictor of clinical outcome., Conclusion: Enhanced expression of proline biosynthetic enzymes promotes HCC cell proliferation. Inhibition of PYCR1 or ALDH18A1 may be a novel therapeutic strategy to target HCC., Lay Summary: Even with the recently approved immunotherapies against liver cancer, currently available medications show limited clinical benefits or efficacy in the majority of patients. As such, it remains a top priority to discover new targets for effective liver cancer treatment. Here, we identify a critical role for the proline biosynthetic pathway in liver cancer development, and demonstrate that targeting key proteins in the pathway, namely PYCR1 and ALDH18A1, may be a novel therapeutic strategy for liver cancer., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
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12. ENPP1 Mutation Causes Recessive Cole Disease by Altering Melanogenesis.
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Chourabi M, Liew MS, Lim S, H'mida-Ben Brahim D, Boussofara L, Dai L, Wong PM, Foo JN, Sriha B, Robinson KS, Denil S, Common JE, Mamaï O, Ben Khalifa Y, Bollen M, Liu J, Denguezli M, Bonnard C, Saad A, and Reversade B
- Subjects
- Biopsy, Cysteine genetics, DNA Mutational Analysis, Female, Fibroblasts, Germ-Line Mutation, HEK293 Cells, Homozygote, Humans, Hypopigmentation diagnosis, Hypopigmentation pathology, Keratinocytes metabolism, Keratoderma, Palmoplantar diagnosis, Keratoderma, Palmoplantar pathology, Male, Pedigree, Phosphoric Diester Hydrolases metabolism, Primary Cell Culture, Pyrophosphatases metabolism, Severity of Illness Index, Skin cytology, Skin pathology, Exome Sequencing, Hypopigmentation genetics, Keratoderma, Palmoplantar genetics, Melanins biosynthesis, Melanocytes metabolism, Phosphoric Diester Hydrolases genetics, Pyrophosphatases genetics
- Abstract
Cole disease is a genodermatosis of pigmentation following a strict dominant mode of inheritance. In this study, we investigated eight patients affected with an overlapping genodermatosis after recessive inheritance. The patients presented with hypo- and hyperpigmented macules over the body, resembling dyschromatosis universalis hereditaria in addition to punctuate palmoplantar keratosis. By homozygosity mapping and whole-exome sequencing, a biallelic p.Cys120Arg mutation in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was identified in all patients. We found that this mutation, like those causing dominant Cole disease, impairs homodimerization of the ENPP1 enzyme that is mediated by its two somatomedin-B-like domains. Histological analysis revealed structural and molecular changes in affected skin that were likely to originate from defective melanocytes because keratinocytes do not express ENPP1. Consistently, RNA-sequencing analysis of patient-derived primary melanocytes revealed alterations in melanocyte development and in pigmentation signaling pathways. We therefore conclude that germline ENPP1 cysteine-specific mutations, primarily affecting the melanocyte lineage, cause a clinical spectrum of dyschromatosis, in which the p.Cys120Arg allele represents a recessive and more severe form of Cole disease., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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13. Below-Ground Attack by the Root Knot Nematode Meloidogyne graminicola Predisposes Rice to Blast Disease.
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Kyndt T, Zemene HY, Haeck A, Singh R, De Vleesschauwer D, Denil S, De Meyer T, Höfte M, Demeestere K, and Gheysen G
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- Animals, Gene Expression Profiling, Gene Expression Regulation, Plant, Indoleacetic Acids metabolism, Magnaporthe physiology, Oryza genetics, Oryza microbiology, Oxidative Stress, Plant Diseases genetics, Plant Growth Regulators metabolism, Plant Roots genetics, Plant Shoots physiology, Transcriptome genetics, Oryza parasitology, Plant Diseases parasitology, Plant Roots parasitology, Tylenchoidea physiology
- Abstract
Magnaporthe oryzae (rice blast) and the root-knot nematode Meloidogyne graminicola are causing two of the most important pathogenic diseases jeopardizing rice production. Here, we show that root-knot nematode infestation on rice roots leads to important above-ground changes in plant immunity gene expression, which is correlated with significantly enhanced susceptibility to blast disease. A detailed metabolic analysis of oxidative stress responses and hormonal balances demonstrates that the above-ground tissues have a disturbed oxidative stress level, with accumulation of H
2 O2 , as well as hormonal disturbances. Moreover, double infection experiments on an oxidative stress mutant and an auxin-deficient rice line indicate that the accumulation of auxin in the above-ground tissue is at least partly responsible for the blast-promoting effect of root-knot nematode infection.- Published
- 2017
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14. Identification and validation of WISP1 as an epigenetic regulator of metastasis in oral squamous cell carcinoma.
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Clausen MJ, Melchers LJ, Mastik MF, Slagter-Menkema L, Groen HJ, van der Laan BF, van Criekinge W, de Meyer T, Denil S, Wisman GB, Roodenburg JL, and Schuuring E
- Subjects
- Adult, Aged, Aged, 80 and over, CCN Intercellular Signaling Proteins metabolism, Carcinoma, Squamous Cell metabolism, Epigenesis, Genetic, Female, Gene Expression Regulation, Neoplastic, Humans, Lymphatic Metastasis, Male, Middle Aged, Mouth Neoplasms metabolism, Prognosis, Promoter Regions, Genetic, Proto-Oncogene Proteins metabolism, Sequence Analysis, DNA, Survival Analysis, CCN Intercellular Signaling Proteins genetics, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, DNA Methylation, Mouth Neoplasms genetics, Mouth Neoplasms pathology, Proto-Oncogene Proteins genetics
- Abstract
Lymph node (LN) metastasis is the most important prognostic factor in oral squamous cell carcinoma (OSCC) patients. However, in approximately one third of OSCC patients nodal metastases remain undetected, and thus are not adequately treated. Therefore, clinical assessment of LN metastasis needs to be improved. The purpose of this study was to identify DNA methylation biomarkers to predict LN metastases in OSCC. Genome wide methylation assessment was performed on six OSCC with (N+) and six without LN metastases (N0). Differentially methylated sequences were selected based on the likelihood of differential methylation and validated using an independent OSCC cohort as well as OSCC from The Cancer Genome Atlas (TCGA). Expression of WISP1 using immunohistochemistry was analyzed on a large OSCC cohort (n = 204). MethylCap-Seq analysis revealed 268 differentially methylated markers. WISP1 was the highest ranking annotated gene that showed hypomethylation in the N+ group. Bisulfite pyrosequencing confirmed significant hypomethylation within the WISP1 promoter region in N+ OSCC (P = 0.03) and showed an association between WISP1 hypomethylation and high WISP1 expression (P = 0.01). Both these results were confirmed using 148 OSCC retrieved from the TCGA database. In a large OSCC cohort, high WISP1 expression was associated with LN metastasis (P = 0.05), disease-specific survival (P = 0.022), and regional disease-free survival (P = 0.027). These data suggest that WISP1 expression is regulated by methylation and WISP1 hypomethylation contributes to LN metastasis in OSCC. WISP1 is a potential biomarker to predict the presence of LN metastases., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2016
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15. SNP-guided identification of monoallelic DNA-methylation events from enrichment-based sequencing data.
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Steyaert S, Van Criekinge W, De Paepe A, Denil S, Mensaert K, Vandepitte K, Vanden Berghe W, Trooskens G, and De Meyer T
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- Genetic Loci, Genomics, Humans, Sequence Analysis, RNA, Alleles, DNA Methylation, Polymorphism, Single Nucleotide, Sequence Analysis, DNA methods
- Abstract
Monoallelic gene expression is typically initiated early in the development of an organism. Dysregulation of monoallelic gene expression has already been linked to several non-Mendelian inherited genetic disorders. In humans, DNA-methylation is deemed to be an important regulator of monoallelic gene expression, but only few examples are known. One important reason is that current, cost-affordable truly genome-wide methods to assess DNA-methylation are based on sequencing post-enrichment. Here, we present a new methodology based on classical population genetic theory, i.e. the Hardy-Weinberg theorem, that combines methylomic data from MethylCap-seq with associated SNP profiles to identify monoallelically methylated loci. Applied on 334 MethylCap-seq samples of very diverse origin, this resulted in the identification of 80 genomic regions featured by monoallelic DNA-methylation. Of these 80 loci, 49 are located in genic regions of which 25 have already been linked to imprinting. Further analysis revealed statistically significant enrichment of these loci in promoter regions, further establishing the relevance and usefulness of the method. Additional validation was done using both 14 whole-genome bisulfite sequencing data sets and 16 mRNA-seq data sets. Importantly, the developed approach can be easily applied to other enrichment-based sequencing technologies, like the ChIP-seq-based identification of monoallelic histone modifications., (© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2014
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16. Systemic suppression of the shoot metabolism upon rice root nematode infection.
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Kyndt T, Denil S, Bauters L, Van Criekinge W, and De Meyer T
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- Animals, Base Sequence, Chlorophyll metabolism, Chlorophyll A, Gene Expression Profiling, Gene Expression Regulation, Plant, Genes, Plant, Oryza genetics, Plant Diseases genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Reproducibility of Results, Reverse Transcriptase Polymerase Chain Reaction, Transcriptome genetics, Oryza parasitology, Plant Diseases parasitology, Plant Roots parasitology, Plant Shoots metabolism, Tylenchoidea physiology
- Abstract
Hirschmanniella oryzae is the most common plant-parasitic nematode in flooded rice cultivation systems. These migratory animals penetrate the plant roots and feed on the root cells, creating large cavities, extensive root necrosis and rotting. The objective of this study was to investigate the systemic response of the rice plant upon root infection by this nematode. RNA sequencing was applied on the above-ground parts of the rice plants at 3 and 7 days post inoculation. The data revealed significant modifications in the primary metabolism of the plant shoot, with a general suppression of for instance chlorophyll biosynthesis, the brassinosteroid pathway, and amino acid production. In the secondary metabolism, we detected a repression of the isoprenoid and shikimate pathways. These molecular changes can have dramatic consequences for the growth and yield of the rice plants, and could potentially change their susceptibility to above-ground pathogens and pests.
- Published
- 2014
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17. Next-generation technologies and data analytical approaches for epigenomics.
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Mensaert K, Denil S, Trooskens G, Van Criekinge W, Thas O, and De Meyer T
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- Animals, Chromatin Immunoprecipitation, Computational Biology methods, DNA Methylation, Environmental Exposure, Humans, Oligonucleotide Array Sequence Analysis methods, Polymerase Chain Reaction methods, RNA, Untranslated genetics, Sequence Analysis, DNA methods, Sulfites chemistry, Epigenesis, Genetic, Epigenomics, Gene Expression Profiling methods, Histones chemistry, Nucleosomes chemistry
- Abstract
Epigenetics refers to the collection of heritable features that modulate the genome-environment interaction without being encoded in the actual DNA sequence. While being mitotically and sometimes even meiotically transmitted, epigenetic traits often demonstrate extensive flexibility. This allows cells to acquire diverse gene expression patterns during differentiation, but also to adapt to a changing environment. However, epigenetic alterations are not always beneficial to the organism, as they are, for example, frequently identified in human diseases such as cancer. Accurate and cost-efficient genome-scale profiling of epigenetic features is thus of major importance to pinpoint these "epimutations," for example, to monitor the epigenetic impact of environmental exposure. Over the last decade, the field of epigenetics has been revolutionized by several innovative "epigenomics" technologies exactly addressing this need. In this review, we discuss and compare widely used next-generation methods to assess DNA methylation and hydroxymethylation, noncoding RNA expression, histone modifications, and nucleosome positioning. Although recent methods are typically based on "second-generation" sequencing, we also pay attention to still commonly used array- and PCR-based methods, and look forward to the additional advantages of single-molecule sequencing. As the current bottleneck in epigenomics research is the analysis rather than generation of data, the basic difficulties and problem-solving strategies regarding data preprocessing and statistical analysis are introduced for the different technologies. Finally, we also consider the complications associated with epigenomic studies of species with yet unsequenced genomes and possible solutions., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2014
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18. A non-genetic, epigenetic-like mechanism of telomere length inheritance?
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De Meyer T, Vandepitte K, Denil S, De Buyzere ML, Rietzschel ER, and Bekaert S
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- Female, Humans, Male, Paternal Age, Pedigree, Telomere genetics, Telomere Shortening genetics
- Published
- 2014
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19. Staphylococcal enterotoxin B influences the DNA methylation pattern in nasal polyp tissue: a preliminary study.
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Pérez-Novo CA, Zhang Y, Denil S, Trooskens G, De Meyer T, Van Criekinge W, Van Cauwenberge P, Zhang L, and Bachert C
- Abstract
Staphylococcal enterotoxins may influence the pro-inflammatory pattern of chronic sinus diseases via epigenetic events. This work intended to investigate the potential of staphylococcal enterotoxin B (SEB) to induce changes in the DNA methylation pattern. Nasal polyp tissue explants were cultured in the presence and absence of SEB; genomic DNA was then isolated and used for whole genome methylation analysis. Results showed that SEB stimulation altered the methylation pattern of gene regions when compared with non stimulated tissue. Data enrichment analysis highlighted two genes: the IKBKB and STAT-5B, both playing a crucial role in T- cell maturation/activation and immune response.
- Published
- 2013
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20. Transcriptional analysis through RNA sequencing of giant cells induced by Meloidogyne graminicola in rice roots.
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Ji H, Gheysen G, Denil S, Lindsey K, Topping JF, Nahar K, Haegeman A, De Vos WH, Trooskens G, Van Criekinge W, De Meyer T, and Kyndt T
- Subjects
- Animals, Homeostasis, Laser Capture Microdissection, Microscopy, Confocal, Molecular Sequence Data, Oryza cytology, Oryza growth & development, Plant Cells metabolism, Plant Growth Regulators metabolism, Plant Roots cytology, Plant Roots genetics, Plant Roots growth & development, Plant Roots metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, RNA, Transcriptome, Oryza genetics, Oryza parasitology, Tylenchoidea physiology
- Abstract
One of the reasons for the progressive yield decline observed in aerobic rice production is the rapid build-up of populations of the rice root knot nematode Meloidogyne graminicola. These nematodes induce specialized feeding cells inside root tissue, called giant cells. By injecting effectors in and sipping metabolites out of these cells, they reprogramme normal cell development and deprive the plant of its nutrients. In this research we have studied the transcriptome of giant cells in rice, after isolation of these cells by laser-capture microdissection. The expression profiles revealed a general induction of primary metabolism inside the giant cells. Although the roots were shielded from light induction, we detected a remarkable induction of genes involved in chloroplast biogenesis and tetrapyrrole synthesis. The presence of chloroplast-like structures inside these dark-grown cells was confirmed by confocal microscopy. On the other hand, genes involved in secondary metabolism and more specifically, the majority of defence-related genes were strongly suppressed in the giant cells. In addition, significant induction of transcripts involved in epigenetic processes was detected inside these cells 7 days after infection.
- Published
- 2013
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21. Quality evaluation of methyl binding domain based kits for enrichment DNA-methylation sequencing.
- Author
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De Meyer T, Mampaey E, Vlemmix M, Denil S, Trooskens G, Renard JP, De Keulenaer S, Dehan P, Menschaert G, and Van Criekinge W
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- Cell Line, Tumor, CpG Islands, Epigenomics methods, Genetic Loci, Humans, Reagent Kits, Diagnostic standards, Reproducibility of Results, Sensitivity and Specificity, DNA Methylation, Sequence Analysis, DNA methods, Sequence Analysis, DNA standards
- Abstract
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.
- Published
- 2013
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22. No shorter telomeres in subjects with a family history of cardiovascular disease in the Asklepios study.
- Author
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De Meyer T, Van Daele CM, De Buyzere ML, Denil S, De Bacquer D, Segers P, Cooman L, De Backer GG, Gillebert TC, Bekaert S, and Rietzschel ER
- Subjects
- Adult, Belgium epidemiology, Family Health, Female, Humans, Leukocytes, Mononuclear ultrastructure, Longitudinal Studies, Male, Middle Aged, Pedigree, Prevalence, Cardiovascular Diseases epidemiology, Cardiovascular Diseases ethnology, Telomere ultrastructure
- Abstract
Objective: Shorter telomere length is associated with the occurrence of cardiovascular events, but the question of causality is complicated by the intertwined effects of inheritance, aging, and lifestyle factors on both telomere length and cardiovascular disease (CVD). Some studies indicated that healthy offspring of coronary artery disease patients exhibited shorter telomeres than subjects without a family history. Importantly, this result would imply that inheritance of shorter telomeres is a primary abnormality associated with an increased risk of CVD, the so-called Telomere Hypothesis of CVD. Therefore, we aimed at further validating the latter results in the large, population-representative Asklepios Study., Methods and Results: Peripheral blood leukocyte telomere length was measured using telomere restriction fragment analysis in the young to middle-aged (≈ 35-55 years old) Asklepios study population, free from overt CVD, and could be successfully combined with data from the Asklepios Family History Database for 2136 subjects. No shorter telomere length could be found in healthy subjects with a family history of CVD compared with those without., Conclusions: These findings cast serious doubt on the hypothesis that telomere length is shorter in families with an increased risk of CVD and do not support the Telomere Hypothesis of CVD.
- Published
- 2012
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23. Transcriptional reprogramming by root knot and migratory nematode infection in rice.
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Kyndt T, Denil S, Haegeman A, Trooskens G, Bauters L, Van Criekinge W, De Meyer T, and Gheysen G
- Subjects
- Animals, Cell Death, Cell Wall genetics, Cell Wall metabolism, Feeding Behavior, Gene Expression Profiling, Genes, Plant, Giant Cells metabolism, Host-Parasite Interactions, Oryza genetics, Plant Roots genetics, Plant Tumors parasitology, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Plant analysis, RNA, Plant genetics, Sequence Analysis, RNA, Signal Transduction, Time Factors, Transcriptome, Tylenchoidea physiology, Gene Expression Regulation, Plant, Oryza parasitology, Plant Roots parasitology, Transcription, Genetic, Tylenchoidea pathogenicity
- Abstract
Rice is one of the most important staple crops worldwide, but its yield is compromised by different pathogens, including plant-parasitic nematodes. In this study we have characterized specific and general responses of rice (Oryza sativa) roots challenged with two endoparasitic nematodes with very different modes of action. Local transcriptional changes in rice roots upon root knot (Meloidogyne graminicola) and root rot nematode (RRN, Hirschmanniella oryzae) infection were studied at two time points (3 and 7 d after infection, dai), using mRNA-seq. Our results confirm that root knot nematodes (RKNs), which feed as sedentary endoparasites, stimulate metabolic pathways in the root, and enhance nutrient transport towards the induced root gall. The migratory RRNs, on the other hand, induce programmed cell death and oxidative stress, and obstruct the normal metabolic activity of the root. While RRN infection causes up-regulation of biotic stress-related genes early in the infection, the sedentary RKNs suppress the local defense pathways (e.g. salicylic acid and ethylene pathways). Interestingly, hormone pathways mainly involved in plant development were strongly induced (gibberellin) or repressed (cytokinin) at 3 dai. These results uncover previously unrecognized nematode-induced expression profiles related to their specific infection strategy., (© 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.)
- Published
- 2012
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