scholarly journals DNA Methylation Changes Induced by Redox-Active Compounds—Choosing the Right PCR-Based Method

Proceedings ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 20
Author(s):  
Patrycja Jakubek ◽  
Jovana Rajić ◽  
Monika Baranowska ◽  
Melita Vidaković ◽  
Agnieszka Bartoszek ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Ht29 Cell ◽  
Pcr Array ◽  
Down Regulation ◽  
Redox Active ◽  
The Right ◽  
Methylation Patterns ◽  
The Impact ◽  
Proper Strategy ◽  
Ht29 Cell Line

The impact of catechins on the expression profile of redox-related genes in HT29 cell line has been studied recently by our group using Oxidative Stress RT2 Profiler PCR Array. Within the examined panel of 84 genes, the down-regulation of SRXN1 gene was unique among other up-regulated genes. We hypothesized that the observed down-regulation resulted from DNA methylation and have exploited this observation to choose the proper strategy to monitor the changes in DNA methylation patterns incurred by dietary antioxidants. The current study verified two PCR-based approaches.

Stage-differentiated modelling of DNA methylation landscapes uncovers salient biomarkers and prognostic signatures in colorectal cancer progression

2021 ◽  
Author(s):  
Sangeetha Muthamilselvan ◽  
Abirami Raghavendran ◽  
Ashok Palaniappan
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cpg Island ◽  
Early Stage ◽  
P Value ◽  
Consensus Analysis ◽  
One Stage ◽  
Differentially Methylated Genes ◽  
Methylation Patterns ◽  
The Impact

Abstract Background: Aberrant DNA methylation acts epigenetically to skew the gene transcription rate up or down, with causative roles in the etiology of cancers. However research on the role of DNA methylation in driving the progression of cancers is limited. In this study, we have developed a comprehensive computational framework for the stage-differentiated modelling of DNA methylation landscapes in colorectal cancer (CRC), and unravelled significant stagewise signposts of CRC progression. Methods: The methylation β - matrix was derived from the public-domain TCGA data, converted into M-value matrix, annotated with AJCC stages, and analysed for stage-salient genes using multiple approaches involving stage-differentiated linear modelling of methylation patterns and/or expression patterns. Differentially methylated genes (DMGs) were identified using a contrast against controls (adjusted p-value <0.001 and |log fold-change of M-value| >2). These results were filtered using a series of all possible pairwise stage contrasts (p-value <0.05) to obtain stage-salient DMGs. These were then subjected to a consensus analysis, followed by Kaplan–Meier survival analysis to evaluate the impact of methylation patterns of consensus stage-salient biomarkers on disease prognosis.Results: We found significant genome-wide changes in methylation patterns in cancer cases relative to controls agnostic of stage. Our stage-differentiated analysis yielded the following stage-salient genes: one stage-I gene (FBN1), one stage-II gene (FOXG1), one stage-III gene (HCN1) and four stage-IV genes (NELL1, ZNF135, FAM123A, LAMA1). All the biomarkers were hypermethylated, indicating down-regulation and signifying a CpG island Methylator Phenotype (CIMP) manifestation. A significant prognostic signature consisting of FBN1 and FOXG1 survived all the steps of our analysis pipeline, and represents a novel early-stage biomarker. Conclusions: We have designed a workflow for stage-differentiated consensus analysis, and identified stage-salient diagnostic biomarkers and an early-stage prognostic biomarker panel. Our studies further yield a novel CIMP-like signature of potential clinical import underlying CRC progression.

scholarly journals The Impact of Natural Dietary Compounds and Food-Borne Mycotoxins on DNA Methylation and Cancer

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2004 ◽  
Author(s):  
Terisha Ghazi ◽  
Thilona Arumugam ◽  
Ashmika Foolchand ◽  
Anil A. Chuturgoon
Keyword(s):  
Dna Methylation ◽  
Bioactive Compounds ◽  
Epigenetic Modification ◽  
Bioactive Molecules ◽  
Methyl Donors ◽  
Food Borne ◽  
One Carbon Metabolism ◽  
Aberrant Dna Methylation ◽  
Methylation Patterns ◽  
The Impact

Cancer initiation and progression is an accumulation of genetic and epigenetic modifications. DNA methylation is a common epigenetic modification that regulates gene expression, and aberrant DNA methylation patterns are considered a hallmark of cancer. The human diet is a source of micronutrients, bioactive molecules, and mycotoxins that have the ability to alter DNA methylation patterns and are thus a contributing factor for both the prevention and onset of cancer. Micronutrients such as betaine, choline, folate, and methionine serve as cofactors or methyl donors for one-carbon metabolism and other DNA methylation reactions. Dietary bioactive compounds such as curcumin, epigallocatechin-3-gallate, genistein, quercetin, resveratrol, and sulforaphane reactivate essential tumor suppressor genes by reversing aberrant DNA methylation patterns, and therefore, they have shown potential against various cancers. In contrast, fungi-contaminated agricultural foods are a source of potent mycotoxins that induce carcinogenesis. In this review, we summarize the existing literature on dietary micronutrients, bioactive compounds, and food-borne mycotoxins that affect DNA methylation patterns and identify their potential in the onset and treatment of cancer.

scholarly journals Developmental subtypes assessed by DNA methylation-iPLEX forecast the natural history of chronic lymphocytic leukemia

Blood ◽  
2019 ◽  
Vol 134 (8) ◽  
pp. 688-698 ◽  
Author(s):  
Brian Giacopelli ◽  
Qiuhong Zhao ◽  
Amy S. Ruppert ◽  
Akwasi Agyeman ◽  
Christoph Weigel ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Chronic Lymphocytic Leukemia ◽  
Risk Stratification ◽  
Kinase Inhibitor ◽  
Lymphocytic Leukemia ◽  
Biological Traits ◽  
Elegant Method ◽  
Mutational Status ◽  
Methylation Patterns ◽  
The Impact

Abstract Alterations in global DNA methylation patterns are a major hallmark of cancer and represent attractive biomarkers for personalized risk stratification. Chronic lymphocytic leukemia (CLL) risk stratification studies typically focus on time to first treatment (TTFT), time to progression (TTP) after treatment, and overall survival (OS). Whereas TTFT risk stratification remains similar over time, TTP and OS have changed dramatically with the introduction of targeted therapies, such as the Bruton tyrosine kinase inhibitor ibrutinib. We have shown that genome-wide DNA methylation patterns in CLL are strongly associated with phenotypic differentiation and patient outcomes. Here, we developed a novel assay, termed methylation-iPLEX (Me-iPLEX), for high-throughput quantification of targeted panels of single cytosine guanine dinucleotides from multiple independent loci. Me-iPLEX was used to classify CLL samples into 1 of 3 known epigenetic subtypes (epitypes). We examined the impact of epitype in 1286 CLL patients from 4 independent cohorts representing a comprehensive view of CLL disease course and therapies. We found that epitype significantly predicted TTFT and OS among newly diagnosed CLL patients. Additionally, epitype predicted TTP and OS with 2 common CLL therapies: chemoimmunotherapy and ibrutinib. Epitype retained significance after stratifying by biologically related biomarkers, immunoglobulin heavy chain mutational status, and ZAP70 expression, as well as other common prognostic markers. Furthermore, among several biological traits enriched between epitypes, we found highly biased immunogenetic features, including IGLV3-21 usage in the poorly characterized intermediate-programmed CLL epitype. In summary, Me-iPLEX is an elegant method to assess epigenetic signatures, including robust classification of CLL epitypes that independently stratify patient risk at diagnosis and time of treatment.

The Impact of Nutritional Interventions in Pregnant Women on DNA Methylation Patterns of the Offspring: A Systematic Review

2018 ◽  
Vol 62 (24) ◽  
pp. 1800034 ◽  
Author(s):  
Stephanie Andraos ◽  
Jamie Violet de Seymour ◽  
Justin Martin O'Sullivan ◽  
Martin Kussmann
Keyword(s):  
Systematic Review ◽  
Dna Methylation ◽  
Pregnant Women ◽  
Nutritional Interventions ◽  
Methylation Patterns ◽  
The Impact

scholarly journals Global DNA Methylation Patterns in Human Gliomas and Their Interplay with Other Epigenetic Modifications

2019 ◽  
Vol 20 (14) ◽  
pp. 3478 ◽  
Author(s):  
Michal J. Dabrowski ◽  
Bartosz Wojtas
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Global Gene Expression ◽  
Global Dna Methylation ◽  
Epigenetic Changes ◽  
Human Gliomas ◽  
Human Pathology ◽  
Different Types ◽  
Methylation Patterns ◽  
The Impact

During the last two decades, several international consortia have been established to unveil the molecular background of human cancers including gliomas. As a result, a huge outbreak of new genetic and epigenetic data appeared. It was not only shown that gliomas share some specific DNA sequence aberrations, but they also present common alterations of chromatin. Many researchers have reported specific epigenetic features, such as DNA methylation and histone modifications being involved in tumor pathobiology. Unlike mutations in DNA, epigenetic changes are more global in nature. Moreover, many studies have shown an interplay between different types of epigenetic changes. Alterations in DNA methylation in gliomas are one of the best described epigenetic changes underlying human pathology. In the following work, we present the state of knowledge about global DNA methylation patterns in gliomas and their interplay with histone modifications that may affect transcription factor binding, global gene expression and chromatin conformation. Apart from summarizing the impact of global DNA methylation on glioma pathobiology, we provide an extract of key mechanisms of DNA methylation machinery.

scholarly journals Molecular Processes Connecting DNA Methylation Patterns with DNA Methyltransferases and Histone Modifications in Mammalian Genomes

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 566 ◽  
Author(s):  
Albert Jeltsch ◽  
Julian Broche ◽  
Pavel Bashtrykov
Keyword(s):  
Dna Methylation ◽  
Chromatin Modification ◽  
Dna Methyltransferases ◽  
Nucleosome Remodeling ◽  
Post Translational Modifications ◽  
Open Questions ◽  
Mammalian Genomes ◽  
Methylation Patterns ◽  
The Impact ◽  
Human And Mouse

DNA methylation is an essential part of the epigenome chromatin modification network, which also comprises several covalent histone protein post-translational modifications. All these modifications are highly interconnected, because the writers and erasers of one mark, DNA methyltransferases (DNMTs) and ten eleven translocation enzymes (TETs) in the case of DNA methylation, are directly or indirectly targeted and regulated by other marks. Here, we have collected information about the genomic distribution and variability of DNA methylation in human and mouse DNA in different genomic elements. After summarizing the impact of DNA methylation on genome evolution including CpG depletion, we describe the connection of DNA methylation with several important histone post-translational modifications, including methylation of H3K4, H3K9, H3K27, and H3K36, but also with nucleosome remodeling. Moreover, we present the mechanistic features of mammalian DNA methyltransferases and their associated factors that mediate the crosstalk between DNA methylation and chromatin modifications. Finally, we describe recent advances regarding the methylation of non-CpG sites, methylation of adenine residues in human cells and methylation of mitochondrial DNA. At several places, we highlight controversial findings or open questions demanding future experimental work.

scholarly journals Down-regulation of BRCA1 in human sporadic breast cancer; analysis of DNA methylation patterns of the putative promoter region

Oncogene ◽  
1998 ◽  
Vol 17 (24) ◽  
pp. 3169-3176 ◽  
Author(s):  
Frédérique Magdinier ◽  
Stéphane Ribieras ◽  
Gilbert M Lenoir ◽  
Lucien Frappart ◽  
Robert Dante
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Promoter Region ◽  
Sporadic Breast Cancer ◽  
Down Regulation ◽  
Putative Promoter ◽  
Putative Promoter Region ◽  
Methylation Patterns
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