scholarly journals DNA methylation in the cancerogenesis process and methods of its detection

2018 ◽  
Vol 74 (6) ◽  
pp. 5982-2018
Author(s):  
EWELINA SEMIK-GURGUL ◽  
TOMASZ ZĄBEK

Epigenetic modifications, apart from affecting gene expression, play an important role in the chromatin structure stabilization, embryonic development and the genomic imprinting. Recent studies have shown that they also play a vital role in other biological processes, including silencing of the expression and mobility of transposable elements and resistance to viral infections by blocking the expression of viral genes. The stability of the genome and the expression of genes in normal cells are strongly dependent on the DNA methylation pattern, which is visibly disturbed in tumor cells. These alterations may be a consequence of the attachment of methyl groups to cytosines in unmethylated DNA sequences, resulting in an increase in the degree of methylation or can be a result of demethylation, i.e. a reduction in the level of DNA methylation. Currently, many techniques are available to determine the level of methylcytosine in DNA, both at the level of single genes and the whole genome. However, each method has its advantages and disadvantages, not being universal in relation to the type of research material and the purpose of planned analyses..

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 912 ◽  
Author(s):  
Scelfo ◽  
Fachinetti

In order to maintain cell and organism homeostasis, the genetic material has to be faithfully and equally inherited through cell divisions while preserving its integrity. Centromeres play an essential task in this process; they are special sites on chromosomes where kinetochores form on repetitive DNA sequences to enable accurate chromosome segregation. Recent evidence suggests that centromeric DNA sequences, and epigenetic regulation of centromeres, have important roles in centromere physiology. In particular, DNA methylation is abundant at the centromere, and aberrant DNA methylation, observed in certain tumors, has been correlated to aneuploidy and genomic instability. In this review, we evaluate past and current insights on the relationship between centromere function and the DNA methylation pattern of its underlying sequences.


The regulation of transcription and translation of a gene under a given environment is dependent on several factors and epigenetics is one such factor, responsible for the differential expression of several genes in health and in various diseases. DNA methylation, an important epigenetics mechanism has been shown to play a vital role in numerous cellular processes, and the abnormal patterns of methylation have been linked to the number of human diseases. CpG islands, a short stretch of DNA enriched with CpG sites in the 5’ end of a gene, although remains unmethylated but tends to methylate aberrantly upon certain environmental exposures. The methylation of the promoter region bearing transcriptional start sites of those genes that encodes tumor suppressors such as tumor protein p53, retinoblastoma-associated protein 1, tumor protein p16, breast cancer 1 and many more result in the reduced expression of these genes and have been implicated in a large number of cancers like retinoblastoma, colon, lung and ovarian. A growing number of human diseases have been found to be associated with the aberrant DNA methylation. Hence, a deep insight into the individual’s epigenetic profile is the need of the hour. Several approaches have been developed to map DNA methylation patterns genome-wide. Some of these approaches include enzymatic digestion with methylation-sensitive restriction enzymes, the capture of 5-mC by methylated DNA-binding proteins followed by nextgeneration sequencing and methyl-DNA immunoprecipitation followed by sequencing of precipitated fragments. However, this chapter is going to describe the most recommended method for studying DNA methylation pattern, the method based on bisulfite sequencing. The bisulfite treatment of DNA converts unmethylated cytosine(s) to uracil(s), which are subsequently amplified as Ts by PCR. Hence, the bisulfitetreated DNA has mutations specifically at unmethylated Cs that can be mapped by Next-Generation sequencing.


2019 ◽  
Vol 4 (3) ◽  
pp. 51-57 ◽  
Author(s):  
Mohammad Hadi Karbalaie Niya ◽  
Naeimeh Roshan-zamir ◽  
Elham Mortazavi

DNA methylation is known as an important epigenetic change in plants and vertebrates genome. In this process, the methyl group transferred by DNA methyl transferase enzymes to cytosine at carbon residue 5 often in the CpG dinucleotide context. DNA methylation plays an important role in the natural development of the organism, genome stability maintenance and processes such as genomic imprinting and chromosome X inactivation in mammals. In addition, changes in DNA methylation pattern have seen in many diseases, including cancer. Analysis of DNA methylation has been useful for rapid disease diagnosis and progression. In recent decades, a revolution has taken place in the methods of DNA methylation analysis, and it is possible to study the pattern of gene methylation at a widespread, short and high resolution level. These methods can be divided into three general categories: (1) cut-based methods by methylation-sensitive enzymes; (2) sodium bisulfide based methods; (3) antibody based methods. Since the existence of different methods makes it difficult to select the appropriate approach, in this review, a number of common methods for examining the methylation pattern with the advantages and disadvantages will be discussed.


2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.


2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler

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)


2020 ◽  
Vol 20 ◽  
Author(s):  
Ezzatollah Fathi ◽  
Raheleh Farahzadi ◽  
Soheila Montazersaheb ◽  
Yasin Bagheri

Background:: Epigenetic modification pattern is considered as a characteristic feature in blood malignancies. Modifications in the DNA methylation modulators are recurrent in lymphoma and leukemia, so that, the distinct methylation pattern defines different types of leukemia. Generally, the role of epigenetics is less understood and most investigations are focused on genetic abnormalities and cytogenic studies to develop novel treatments for patients with hematologic disorders. Recently, understanding the underlying mechanism of acute lymphoblastic leukemia (ALL), especially epigenetic altera-tions as a driving force in the development of ALL opens a new era of investigation for developing promising strategy, be-yond available conventional therapy. Objective:: This review will focus on a better understanding of the epigenetic mechanisms in cancer development and pro-gression, with an emphasis on epigenetic alterations in ALL including, DNA methylation, histone modification, and mi-croRNA alterations. Other topics that will be discussed include the use of epigenetic alterations as a promising therapeutic target in order to develop novel well-suited approaches against ALL. Conclusion:: According to the literature review, leukemogenesis of ALL is extensively influenced by epigenetic modifica-tions, particularly DNA hyper-methylation, histone modification, and miRNA alteration.


2020 ◽  
Vol 4 (141) ◽  
pp. 114-122
Author(s):  
DAR’YA LEBEDEVA ◽  
◽  
ANNA KARPUNICHEVA

Large forces and significant thermal effects are created on the rolls when rolling sheets. The higher the stability of the rolls, the less downtime during their rerolling and higher productivity. (Research purpose) The research purpose is in analyzing the ways of restoring rolls and choose the most appropriate method for restoring these parts. (Materials and methods) The article presents the analysis of the scientific and technical literature on the topic of rolling production, methods for restoring large-sized machine parts of machine-building and metallurgical industries that work in difficult conditions and are subject to a high degree of wear. Authors try to solve the problem by means of comparative and logical analysis based on theoretical and empirical methods of scientific research. (Results and discussion) The article presents two groups of methods for restoring rolled rolls: banding and surfacing the working layer of the roll. Authors have analyzed each method in terms of technology, equipment, and feasibility. The article presents the advantages and disadvantages of the methods under consideration. (Conclusions) The most acceptable way to restore parts with a high degree of wear is surfacing. It is most efficient to apply submerged surfacing using an additional hot additive. Such surfacing, despite some complication of the equipment design, allows to deposit the metal on the roll with low heat input and in most cases in one pass. Surfacing using an additional hot additive allows to increase the productivity of the process by up to 250 percent while reducing the penetration depth by 2-3 times and saving energy by up to 40 percent.


2019 ◽  
Vol 952 (10) ◽  
pp. 47-54
Author(s):  
A.V. Komissarov ◽  
A.V. Remizov ◽  
M.M. Shlyakhova ◽  
K.K. Yambaev

The authors consider hand-held laser scanners, as a new photogrammetric tool for obtaining three-dimensional models of objects. The principle of their work and the newest optical systems based on various sensors measuring the depth of space are described in detail. The method of simultaneous navigation and mapping (SLAM) used for combining single scans into point cloud is outlined. The formulated tasks and methods for performing studies of the DotProduct (USA) hand-held laser scanner DPI?8X based on a test site survey are presented. The accuracy requirements for determining the coordinates of polygon points are given. The essence of the performed experimental research of the DPI?8X scanner is described, including scanning of a test object at various scanner distances, shooting a test polygon from various scanner positions and building point cloud, repeatedly shooting the same area of the polygon to check the stability of the scanner. The data on the assessment of accuracy and analysis of research results are given. Fields of applying hand-held laser scanners, their advantages and disadvantages are identified.


Zygote ◽  
2021 ◽  
pp. 1-6
Author(s):  
Liliana Burlibaşa ◽  
Alina-Teodora Nicu ◽  
Carmen Domnariu

Summary The process of cytodifferentiation in spermatogenesis is governed by a unique genetic and molecular programme. In this context, accurate ‘tuning’ of the regulatory mechanisms involved in germ cells differentiation is required, as any error could have dramatic consequences on species survival and maintenance. To study the processes that govern the spatial–temporal expression of genes, as well as analyse transmission of epigenetic information to descendants, an integrated approach of genetics, biochemistry and cytology data is necessary. As information in the literature on interplay between DNA methylation and histone H3 lysine 4 trimethylation (H3K4me3) in the advanced stages of murine spermatogenesis is still scarce, we investigated the effect of a DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine, at the cytological level using immunocytochemistry methodology. Our results revealed a particular distribution of H3K4me3 during sperm cell differentiation and highlighted an important role for regulation of DNA methylation in controlling histone methylation and chromatin remodelling during spermatogenesis.


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