DNA methylation and genomic imprinting: insights from cancer into epigenetic mechanisms

2002 ◽  
Vol 12 (5) ◽  
pp. 389-398 ◽  
Author(s):  
Andrew P Feinberg ◽  
Hengmi Cui ◽  
Rolf Ohlsson
2012 ◽  
Vol 10 (3) ◽  
pp. 59-76
Author(s):  
Lilia R Kutlyeva ◽  
Irina R Gilayzova ◽  
Rita I Khusainova ◽  
Elsa K Khusnutdinova

Epigenetic mechanisms of gene regulation play a key role in carcinogenesis. This review will focus on the recent advances of epigenetic investigations in the development of human cancer. The role of histone modifications, genomic imprinting and DNA methylation in renal cell carcinoma development and progression will be considered.


2016 ◽  
Vol 4 (1) ◽  
pp. 181-184 ◽  
Author(s):  
Emirjeta Bajrami ◽  
Mirko Spiroski

BACKGROUND: Genomic imprinting is the inheritance out of Mendelian borders. Many of inherited diseases and human development violates Mendelian law of inheritance, this way of inheriting is studied by epigenetics.AIM: The aim of this review is to analyze current opinions and options regarding to this way of inheriting.RESULTS: Epigenetics shows that gene expression undergoes changes more complex than modifications in the DNA sequence; it includes the environmental influence on the gametes before conception. Humans inherit two alleles from mother and father, both are functional for the majority of the genes, but sometimes one is turned off or “stamped” and doesn’t show in offspring, that gene is imprinted. Imprinting means that that gene is silenced, and gene from other parent is expressed. The mechanisms for imprinting are still incompletely defined, but they involve epigenetic modifications that are erased and then reset during the creation of eggs and sperm. Genomic imprinting is a process of silencing genes through DNA methylation. The repressed allele is methylated, while the active allele is unmethylated. The most well-known conditions include Prader-Willi syndrome, and Angelman syndrome. Both of these syndromes can be caused by imprinting or other errors involving genes on the long arm of chromosome 15.CONCLUSIONS: Genomic imprinting and other epigenetic mechanisms such as environment is shown that plays role in offspring neurodevelopment and autism spectrum disorder.


2019 ◽  
Vol 20 (7) ◽  
pp. 727-735 ◽  
Author(s):  
Yi Wu ◽  
Zhibin Cheng ◽  
Yueyu Bai ◽  
Xi Ma

Nutrients can regulate metabolic activities of living organisms through epigenetic mechanisms, including DNA methylation, histone modification, and RNA regulation. Since the nutrients required for early embryos and postpartum lactation are derived in whole or in part from maternal and lactating nutrition, the maternal nutritional level affects the growth and development of fetus and creates a profound relationship between disease development and early environmental exposure in the offspring’s later life. Protein is one of the most important biological macromolecules, involved in almost every process of life, such as information transmission, energy processing and material metabolism. Maternal protein intake levels may affect the integrity of the fetal genome and alter DNA methylation and gene expression. Most amino acids are supplied to the fetus from the maternal circulation through active transport of placenta. Some amino acids, such as methionine, as dietary methyl donor, play an important role in DNA methylation and body’s one-carbon metabolism. The purpose of this review is to describe effects of maternal dietary protein and amino acid intake on fetal and neonatal growth and development through epigenetic mechanisms, with examples in humans and animals.


2019 ◽  
Vol 16 (4) ◽  
pp. 386-391 ◽  
Author(s):  
Kenneth Lundstrom

Epigenetic mechanisms comprising of DNA methylation, histone modifications and gene silencing by RNA interference have been strongly linked to the development and progression of various diseases. These findings have triggered research on epigenetic functions and signal pathways as targets for novel drug discovery. Dietary intake has also presented significant influence on human health and disease development and nutritional modifications have proven important in prevention, but also the treatment of disease. Moreover, a strong link between nutrition and epigenetic changes has been established. Therefore, in attempts to develop novel safer and more efficacious drugs, both nutritional requirements and epigenetic mechanisms need to be addressed.


Epigenomes ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 18
Author(s):  
Murat Toruner ◽  
Martin E. Fernandez-Zapico ◽  
Christopher L. Pin

Pancreatic cancer remains among the deadliest forms of cancer with a 5 year survival rate less than 10%. With increasing numbers being observed, there is an urgent need to elucidate the pathogenesis of pancreatic cancer. While both contribute to disease progression, neither genetic nor environmental factors completely explain susceptibility or pathogenesis. Defining the links between genetic and environmental events represents an opportunity to understand the pathogenesis of pancreatic cancer. Epigenetics, the study of mitotically heritable changes in genome function without a change in nucleotide sequence, is an emerging field of research in pancreatic cancer. The main epigenetic mechanisms include DNA methylation, histone modifications and RNA interference, all of which are altered by changes to the environment. Epigenetic mechanisms are being investigated to clarify the underlying pathogenesis of pancreatic cancer including an increasing number of studies examining the role as possible diagnostic and prognostic biomarkers. These mechanisms also provide targets for promising new therapeutic approaches for this devastating malignancy.


Endocrinology ◽  
2013 ◽  
Vol 154 (8) ◽  
pp. 2881-2890 ◽  
Author(s):  
Yang Zhang ◽  
Shen Zhang ◽  
Zhixin Liu ◽  
Lihong Zhang ◽  
Weimin Zhang

Abstract In vertebrates, cytochrome P450 aromatase, encoded by cyp19a1, converts androgens to estrogens and plays important roles in gonadal differentiation and development. The present study examines whether epigenetic mechanisms are involved in cyp19a1a expression and subsequent gonadal development in the hermaphroditic ricefield eel. The expression of the ricefield eel cyp19a1a was stimulated by gonadotropin via the cAMP pathway in the ovary but not the ovotestis or testis. The CpG within the cAMP response element (CRE) of the cyp19a1a promoter was hypermethylated in the ovotestis and testis compared with the ovary. The methylation levels of CpG sites around CRE in the distal region (region II) and around steroidogenic factor 1/adrenal 4 binding protein sites and TATA box in the proximal region (region I) were inversely correlated with cyp19a1a expression during the natural sex change from female to male. In vitro DNA methylation decreased the basal and forskolin-induced activities of cyp19a1a promoter. Chromatin immunoprecipitation assays indicated that histone 3 (Lys9) in both regions I and II of the cyp19a1a promoter were deacetylated and trimethylated in the testis, and in contrast to the ovary, phosphorylated CRE-binding protein failed to bind to these regions. Lastly, the DNA methylation inhibitor 5-aza-2′-deoxycytidine reversed the natural sex change of ricefield eels. These results suggested that epigenetic mechanisms involving DNA methylation and histone deacetylation and methylation may abrogate the stimulation of cyp19a1a by gonadotropins in a male-specific fashion. This may be a mechanism widely used to drive natural sex change in teleosts as well as gonadal differentiation in other vertebrates.


Reproduction ◽  
2010 ◽  
Vol 140 (3) ◽  
pp. 411-423 ◽  
Author(s):  
Philippe Arnaud

The cis-acting regulatory sequences of imprinted gene loci, called imprinting control regions (ICRs), acquire specific imprint marks in germ cells, including DNA methylation. These epigenetic imprints ensure that imprinted genes are expressed exclusively from either the paternal or the maternal allele in offspring. The last few years have witnessed a rapid increase in studies on how and when ICRs become marked by and subsequently maintain such epigenetic modifications. These novel findings are summarised in this review, which focuses on the germline acquisition of DNA methylation imprints and particularly on the combined role of primary sequence specificity, chromatin configuration, non-histone proteins and transcriptional events.


2021 ◽  
Vol 28 ◽  
Author(s):  
Chunyan Ao ◽  
Lin Gao ◽  
Liang Yu

: DNA methylation is an important mode of regulation in epigenetic mechanisms, and it is one of the research foci in the field of epigenetics. DNA methylation modification affects a series of biological processes, such as eukaryotic cell growth, differentiation and transformation mechanisms, by regulating gene expression. In this review, we systematically summarized the DNA methylation databases, prediction tools for DNA methylation modification, machine learning algorithms for predicting DNA methylation modification, and the relationship between DNA methylation modification and diseases such as hypertension, Alzheimer's disease, diabetic nephropathy, and cancer. An in-depth understanding of DNA methylation mechanisms can promote accurate prediction of DNA methylation modifications and the treatment and diagnosis of related diseases.


2020 ◽  
Vol 53 (383) ◽  
pp. MISC1-MISC3
Author(s):  
Andrea Maugeri

Retinal degenerative diseases are the leading causes of blindness and low vision among working-age and older adults worldwide, with 170 and 130 million individuals suffering from age-related macular degeneration (AMD) and diabetic retinopathy, respectively. Although several studies began to show benefits from dietary interventions against retinal degenerative disease, an integrated approach is needed to understand molecular mechanisms underpinning the protective or risky effect of dietary factors. A specific area of research that elucidates mechanisms involved in gene-diet interaction is the Nutri-epigenomics, the study of the impact of diet on gene expression by modulating epigenetic mechanisms. The present research investigated the role of DNA methylation – one of the most commonly analysed epigenetic mechanisms - in the pathophysiology of retinal degenerative diseases, by exploiting a multiple integrated approach. In vitro studies initially helped us to understand how pathological features of retinal degeneration (e.g. oxidative stress, inflammation and hyperglycaemia) modulated functions of enzymes involved in the methylation of Long Interspersed Nuclear Element 1 (LINE-1) sequences in retinal cells. We also proved that some nutrients (e.g. resveratrol and curcumin) might counteract these effects and restore DNA methylation level in retinal cells under oxidative, inflammatory and high glucose conditions. We further analysed whether LINE-1 methylation level differed between patients with AMD and controls without posterior segment eye diseases. Interestingly, we noted a significant difference between the two groups, with higher LINE-1 methylation level in blood samples from AMD patients. This evidence -albeit promising for biomarker discovery- requires confirmation by further large-size prospective studies taking into account different factors. Our research, in fact, also suggested that the risk of retinal degenerative diseases derives from the combination of genetic risk variants, clinical characteristics, environmental exposures and unhealthy lifestyles, which in turn are interrelated. Thus, it would be interesting to study how the exposome -the totality of exposures individuals experience over the course of life- might induce epigenetic mechanisms able to reduce or increase the risk for retinal degenerative diseases.


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