A role for poly(ADP-ribosyl)ation in DNA methylation

2003 ◽  
Vol 81 (3) ◽  
pp. 197-208 ◽  
Author(s):  
Giuseppe Zardo ◽  
Anna Reale ◽  
Giovanna De Matteis ◽  
Serena Buontempo ◽  
Paola Caiafa
Keyword(s):  
Dna Methylation ◽  
Gene Silencing ◽  
Control Mechanism ◽  
Epigenetic Modification ◽  
Housekeeping Genes ◽  
Promoter Regions ◽  
Epigenetic Events ◽  
Aberrant Dna Methylation ◽  
Methylation Patterns ◽  
Histone Methylation And Acetylation

The aberrant DNA methylation of promoter regions of housekeeping genes leads to gene silencing. Additional epigenetic events, such as histone methylation and acetylation, also play a very important role in the definitive repression of gene expression by DNA methylation. If the aberrant DNA methylation of promoter regions is the starting or the secondary event leading to the gene silencing is still debated. Mechanisms controlling DNA methylation patterns do exist although they have not been ultimately proven. Our data suggest that poly(ADP-ribosyl)ation might be part of this control mechanism. Thus an additional epigenetic modification seems to be involved in maintaining tissue and cell-type methylation patterns that when formed during embryo development, have to be rigorously conserved in adult organisms.Key words: DNA methylation, chromatin, poly(ADP-ribosyl)ation.

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 PCR-Based Methods for Detecting Single-Locus DNA Methylation Biomarkers in Cancer Diagnostics, Prognostics, and Response to Treatment

2009 ◽  
Vol 55 (8) ◽  
pp. 1471-1483 ◽  
Author(s):  
Lasse Sommer Kristensen ◽  
Lise Lotte Hansen
Keyword(s):  
Dna Methylation ◽  
Epigenetic Modification ◽  
Cancer Diagnostics ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Diagnostic Tools ◽  
Promoter Regions ◽  
Advantages And Disadvantages ◽  
Specific Pcr ◽  
Methylation Patterns

Abstract Background: DNA methylation is a highly characterized epigenetic modification of the human genome that is implicated in cancer. The altered DNA methylation patterns found in cancer cells include not only global hypomethylation but also discrete hypermethylation of specific genes. In particular, numerous tumor suppressor genes undergo epigenetic silencing because of hypermethylated promoter regions. Some of these genes are considered promising DNA methylation biomarkers for early cancer diagnostics, and some have been shown to be valuable for predicting prognosis or the response to therapy. Content: PCR-based methods that use sodium bisulfite–treated DNA as a template are generally accepted as the most analytically sensitive and specific techniques for analyzing DNA methylation at single loci. A number of new methods, such as methylation-specific fluorescent amplicon generation (MS-FLAG), methylation-sensitive high-resolution melting (MS-HRM), and sensitive melting analysis after real-time methylation-specific PCR (SMART-MSP), now complement the traditional PCR-based methods and promise to be valuable diagnostic tools. In particular, the HRM technique shows great potential as a diagnostic tool because of its closed-tube format and cost-effectiveness. Summary: Numerous traditional and new PCR-based methods have been developed for detecting DNA methylation at single loci. All have characteristic advantages and disadvantages, particularly with regard to use in clinical settings.

scholarly journals The DNA methylation landscape of five pediatric-tumor types

2021 ◽  
Author(s):  
Alyssa C Parker ◽  
Badí I Quinteros ◽  
Stephen R Piccolo
Keyword(s):  
Dna Methylation ◽  
Pediatric Cancer ◽  
Cancer Type ◽  
Pediatric Tumors ◽  
Promoter Regions ◽  
Pediatric Tumor ◽  
Aberrant Dna Methylation ◽  
Rhabdoid Tumors ◽  
Tumor Types ◽  
Methylation Patterns

Fewer DNA mutations have been identified in pediatric tumors than adult tumors, suggesting that alternative tumorigenic mechanisms, including aberrant DNA methylation, may play a prominent role in pediatric tumors. Methylation is an epigenetic process of regulating gene expression in which methyl groups are attached to DNA molecules, often in promoter regions. In Wilms tumors and acute myeloid leukemias, increased levels of epigenetic silencing have been associated with worse patient outcomes. However, to date, researchers have studied methylation primarily in adult tumors and for specific genes but not on a pan-pediatric cancer scale. We addressed these gaps first by aggregating methylation data from 309 noncancerous samples and establishing baseline expectations for each gene. Even though these samples represent diverse tissue types and population ancestral groups, methylation levels were highly consistent for most genes. Second, we compared tumor methylation levels against these baseline values for five pediatric cancer types--Wilms tumors, clear cell sarcomas of the kidney, rhabdoid tumors, neuroblastomas, and osteosarcomas. Hypermethylation was more common than hypomethylation--as many as 11.8% of genes were hypermethylated in a given tumor, compared to a maximum of 4.8% for hypomethylated genes. For each cancer type, genes with the highest variance exhibited consistently divergent methylation patterns for distinct patient subsets. We evaluated whether genomic and epigenomic abnormalities contribute to pediatric tumorigenesis in a mutually exclusive manner but did not find evidence of this phenomenon. Furthermore, even though oncogenes are commonly upregulated in tumors, and tumor-suppressor genes are commonly downregulated in tumors, we did not find statistical evidence that methylation drives such patterns on a broad scale in pediatric tumors.

scholarly journals Gene-Specific Targeting of DNA Methylation in the Mammalian Genome

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1515 ◽  
Author(s):  
Urbano ◽  
Smith ◽  
Weeks ◽  
Chatterjee
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor Genes ◽  
Epigenetic Modification ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Transcription Activator ◽  
Promoter Regions ◽  
Current State ◽  
Aberrant Dna Methylation ◽  
Gene Expression Dysregulation

DNA methylation is the most widely-studied epigenetic modification, playing a critical role in the regulation of gene expression. Dysregulation of DNA methylation is implicated in the pathogenesis of numerous diseases. For example, aberrant DNA methylation in promoter regions of tumor-suppressor genes has been strongly associated with the development and progression of many different tumors. Accordingly, technologies designed to manipulate DNA methylation at specific genomic loci are very important, especially in the context of cancer therapy. Traditionally, epigenomic editing technologies have centered around zinc finger proteins (ZFP)- and transcription activator-like effector protein (TALE)-based targeting. More recently, however, the emergence of clustered regulatory interspaced short palindromic repeats (CRISPR)-deactivated Cas9 (dCas9)-based editing systems have shown to be a more specific and efficient method for the targeted manipulation of DNA methylation. Here, we describe the regulation of the DNA methylome, its significance in cancer and the current state of locus-specific editing technologies for altering DNA methylation.

scholarly journals METHYLATION OF PROLACTIN AND OXYTOCIN HORMONE GENES; PHYSIOLOGICAL FUNCTIONS AND ROLES IN DISEASE STATES

2019 ◽  
Vol 8 (2) ◽  
Author(s):  
Manoj G Tyagi ◽  
Deepak G Shewade ◽  
Megha Chaudhary ◽  
Mohammed I Wani ◽  
Shyam S Yadav
Keyword(s):  
Dna Methylation ◽  
Gene Silencing ◽  
Social Behaviour ◽  
Functional Significance ◽  
Genome Stability ◽  
Epigenetic Modification ◽  
Oxytocin Receptor ◽  
Endocrine Function ◽  
Disease States ◽  
Epigenetic Events

DNA methylation is the key mechanism in epigenetic events involved in gene silencing and gene genome stability. The two important hormones involved in social behaviour, lactation and parturition are Oxytocin and Prolactin. There is growing interest in epigenetic modification of oxytocin and prolactin in neurotransmission interaction and their functional significance. This review outlines the influence of DNA methylation of genes of oxytocin and prolactin hormones/receptors and impact on their biological roles and influence on endocrine function in mammals. Keywords: Prolactin, Oxytocin, receptor, DNA methylation, epigenetics

Examination of the dynamics of global DNA methylation pattern establishment during spermatogenesiss

2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Epigenetic Modification ◽  
Methylation Pattern ◽  
Chromosome 9 ◽  
Specific Gene ◽  
Global Methylation ◽  
Dna Methylation Pattern ◽  
Methylation Patterns

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)

scholarly journals Age-related disturbances in DNA (hydroxy)methylation in APP/PS1 mice

2018 ◽  
Vol 9 (1) ◽  
pp. 190-202 ◽  
Author(s):  
Leonidas Chouliaras ◽  
Roy Lardenoije ◽  
Gunter Kenis ◽  
Diego Mastroeni ◽  
Patrick R. Hof ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Dna Methylation ◽  
Brain Aging ◽  
Wild Type ◽  
Dna Hydroxymethylation ◽  
Quantitative Immunohistochemistry ◽  
Age Related ◽  
Aberrant Dna Methylation ◽  
Methylation Patterns ◽  
Age Related Changes

Abstract Brain aging has been associated with aberrant DNA methylation patterns, and changes in the levels of DNA methylation and associated markers have been observed in the brains of Alzheimer’s disease (AD) patients. DNA hydroxymethylation, however, has been sparsely investigated in aging and AD. We have previously reported robust decreases in 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in the hippocampus of AD patients compared to non-demented controls. In the present study, we investigated 3- and 9-month-old APPswe/PS1ΔE9 transgenic and wild-type mice for possible age-related alterations in 5-mC and 5-hmC levels in three hippocampal sub-regions using quantitative immunohistochemistry. While age-related increases in levels of both 5-mC and 5-hmC were found in wild-type mice, APPswe/PS1ΔE9 mice showed decreased levels of 5-mC at 9 months of age and no age-related changes in 5-hmC throughout the hippocampus. Altogether, these findings suggest that aberrant amyloid processing impact on the balance between DNA methylation and hydroxymethylation in the hippocampus during aging in mice.

scholarly journals Fetal and Neonatal Exposure to the Endocrine Disruptor Methoxychlor Causes Epigenetic Alterations in Adult Ovarian Genes

Endocrinology ◽  
2009 ◽  
Vol 150 (10) ◽  
pp. 4681-4691 ◽  
Author(s):  
Aparna Mahakali Zama ◽  
Mehmet Uzumcu
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Ovarian Function ◽  
Endocrine Disrupting Chemicals ◽  
Neonatal Exposure ◽  
Dna Hypermethylation ◽  
Promoter Regions ◽  
Altered Expression ◽  
Arbitrarily Primed Pcr ◽  
Methylation Patterns

Abstract Exposure to endocrine-disrupting chemicals during development could alter the epigenetic programming of the genome and result in adult-onset disease. Methoxychlor (MXC) and its metabolites possess estrogenic, antiestrogenic, and antiandrogenic activities. Previous studies showed that fetal/neonatal exposure to MXC caused adult ovarian dysfunction due to altered expression of key ovarian genes including estrogen receptor (ER)-β, which was down-regulated, whereas ERα was unaffected. The objective of the current study was to evaluate changes in global and gene-specific methylation patterns in adult ovaries associated with the observed defects. Rats were exposed to MXC (20 μg/kg·d or 100 mg/kg·d) between embryonic d 19 and postnatal d 7. We performed DNA methylation analysis of the known promoters of ERα and ERβ genes in postnatal d 50–60 ovaries using bisulfite sequencing and methylation-specific PCRs. Developmental exposure to MXC led to significant hypermethylation in the ERβ promoter regions (P < 0.05), whereas the ERα promoter was unaffected. We assessed global DNA methylation changes using methylation-sensitive arbitrarily primed PCR and identified 10 genes that were hypermethylated in ovaries from exposed rats. To determine whether the MXC-induced methylation changes were associated with increased DNA methyltransferase (DNMT) levels, we measured the expression levels of Dnmt3a, Dnmt3b, and Dnmt3l using semiquantitative RT-PCR. Whereas Dnmt3a and Dnmt3l were unchanged, Dnmt3b expression was stimulated in ovaries of the 100 mg/kg MXC group (P < 0.05), suggesting that increased DNMT3B may cause DNA hypermethylation in the ovary. Overall, these data suggest that transient exposure to MXC during fetal and neonatal development affects adult ovarian function via altered methylation patterns.

scholarly journals Microwave Assisted DNA Hydrolysis for Global Methylation Analysis by Gas Chromatography/Tandem Mass Spectrometry

2018 ◽  
Vol 62 (2) ◽  
Author(s):  
Karla Viridiana Castro-Cerritos ◽  
Julio Cesar Torres-Elguera ◽  
Jaqueline Capataz-Tafur ◽  
Erick Adrian Juarez-Arellano ◽  
Adolfo Lopez-Torres
Keyword(s):  
Dna Methylation ◽  
Large Scale ◽  
Limit Of Detection ◽  
Multiple Reaction Monitoring ◽  
Good Alternative ◽  
Detection Methods ◽  
Mass Analyzer ◽  
Global Methylation ◽  
Epigenetic Events ◽  
Methylation Patterns

<div><p class="Abstract">The analysis of the global DNA methylation, calculated as the percentage of 5-methylcytosine (5mC) over the total sum of cytosines, is a well stablished biomarker for monitoring large scale epigenetic events in organisms. DNA purification, hydrolysis, separation and detection methods are critical steps to determine this biomarker. In the present work is proposed a robust procedure for DNA acid-hydrolysis assisted by microwave that provides identical DNA methylation patterns that enzymatic hydrolysis and better release of 5mC than acid classic method. The quantification was performed using a gas chromatographer coupled to a mass spectrometer with triple quadrupole as mass analyzer (GC-TQ-MS/MS) using multiple reaction monitoring (MRM) mode for the trimethylsilyl-derivates of nucleobases; following the transitions of 254→238, 240→170 and 254→238, 254→184 (m/z) for C and 5mC respectively, was achieved a limit of detection of 0.46 fmol for C and 0.41 fmol for 5mC. The proposed procedure is capable of determine 0.004% of 5mC in 50 ng of DNA in a chromatographic time of 10 minutes, being a good alternative to LC-MS/MS analysis.</p></div>

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