scholarly journals Aberrant DNA Methylation Mediates the Transgenerational Risk of Metabolic and Chronic Disease Due to Maternal Obesity and Overnutrition

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1653
Author(s):  
Yan Li ◽  
Carol A. Pollock ◽  
Sonia Saad
Keyword(s):  
Dna Methylation ◽  
Animal Studies ◽  
Maternal Obesity ◽  
Metabolic Diseases ◽  
Epigenetic Modification ◽  
Phenotypic Expression ◽  
Health Issues ◽  
Alcoholic Fatty Liver ◽  
Maternal Risks ◽  
Aberrant Dna Methylation

Maternal obesity is a rapidly evolving universal epidemic leading to acute and long-term medical and obstetric health issues, including increased maternal risks of gestational diabetes, hypertension and pre-eclampsia, and the future risks for offspring’s predisposition to metabolic diseases. Epigenetic modification, in particular DNA methylation, represents a mechanism whereby environmental effects impact on the phenotypic expression of human disease. Maternal obesity or overnutrition contributes to the alterations in DNA methylation during early life which, through fetal programming, can predispose the offspring to many metabolic and chronic diseases, such as non-alcoholic fatty liver disease, obesity, diabetes, and chronic kidney disease. This review aims to summarize findings from human and animal studies, which support the role of maternal obesity in fetal programing and the potential benefit of altering DNA methylation to limit maternal obesity related disease in the offspring.

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.

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 Epigenetics and developmental origins of diabetes: correlation or causation?

2018 ◽  
Vol 315 (1) ◽  
pp. E15-E28 ◽  
Author(s):  
Amita Bansal ◽  
Rebecca A. Simmons
Keyword(s):  
Animal Studies ◽  
Metabolic Diseases ◽  
Epigenetic Modification ◽  
Developmental Origins ◽  
Critical Periods ◽  
Metabolic Outcome ◽  
Health And Disease ◽  
Founding Principle ◽  
The Many

The incidence of metabolic disorders like type 2 diabetes (T2D) and obesity continue to increase. Although it is evident that the increasing incidence of diabetes confers a global societal and economic burden, the mechanisms responsible for the increased incidence of T2D are not well understood. Extensive efforts to understand the association of early-life perturbations with later onset of metabolic diseases, the founding principle of developmental origins of health and disease, have been crucial in determining the mechanisms that may be driving the pathogenesis of T2D. As the programming of the epigenome occurs during critical periods of development, it has emerged as a potential molecular mechanism that could occur early in life and impact metabolic health decades later. In this review, we critically evaluate human and animal studies that illustrated an association of epigenetic processes with development of T2D as well as intervention strategies that have been employed to reverse the perturbed epigenetic modification or reprogram the naturally occurring epigenetic marks to favor improved metabolic outcome. We highlight that although our understanding of epigenetics and its contribution toward developmental origins of T2D continues to grow, whether epigenetics is a cause, consequence, or merely a correlation remains debatable due to the many limitations/challenges of the existing epigenetic studies. Finally, we discuss the potential of establishing collaborative research efforts between different disciplines, including physiology, epigenetics, and bioinformatics, to help advance the developmental origins field with great potential for understanding the pathogenesis of T2D and developing preventive strategies for T2D.

scholarly journals Aberrant DNA Methylation in Acute Myeloid Leukemia and Its Clinical Implications

2019 ◽  
Vol 20 (18) ◽  
pp. 4576 ◽  
Author(s):  
Xianwen Yang ◽  
Molly Pui Man Wong ◽  
Ray Kit Ng
Keyword(s):  
Dna Methylation ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Epigenetic Modification ◽  
Critical Role ◽  
Genetic Alterations ◽  
Dna Methyltransferases ◽  
Clinical Implications ◽  
Aberrant Dna Methylation ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a heterogeneous disease that is characterized by distinct cytogenetic or genetic abnormalities. Recent discoveries in cancer epigenetics demonstrated a critical role of epigenetic dysregulation in AML pathogenesis. Unlike genetic alterations, the reversible nature of epigenetic modifications is therapeutically attractive in cancer therapy. DNA methylation is an epigenetic modification that regulates gene expression and plays a pivotal role in mammalian development including hematopoiesis. DNA methyltransferases (DNMTs) and Ten-eleven-translocation (TET) dioxygenases are responsible for the dynamics of DNA methylation. Genetic alterations of DNMTs or TETs disrupt normal hematopoiesis and subsequently result in hematological malignancies. Emerging evidence reveals that the dysregulation of DNA methylation is a key event for AML initiation and progression. Importantly, aberrant DNA methylation is regarded as a hallmark of AML, which is heralded as a powerful epigenetic marker in early diagnosis, prognostic prediction, and therapeutic decision-making. In this review, we summarize the current knowledge of DNA methylation in normal hematopoiesis and AML pathogenesis. We also discuss the clinical implications of DNA methylation and the current therapeutic strategies of targeting DNA methylation in AML therapy.

scholarly journals The emerging roles of DNA methylation in the clinical management of prostate cancer

2006 ◽  
Vol 13 (2) ◽  
pp. 357-377 ◽  
Author(s):  
Antoinette S Perry ◽  
Ruth Foley ◽  
Karen Woodson ◽  
Mark Lawler
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
Clinical Management ◽  
Epigenetic Modification ◽  
Retinoic Acid Receptor ◽  
Promoter Hypermethylation ◽  
Androgen Independence ◽  
Retinoic Acid Receptor Β2 ◽  
Key Issues ◽  
Aberrant Dna Methylation

Aberrant DNA methylation is one of the hallmarks of carcinogenesis and has been recognized in cancer cells for more than 20 years. The role of DNA methylation in malignant transformation of the prostate has been intensely studied, from its contribution to the early stages of tumour development to the advanced stages of androgen independence. The most significant advances have involved the discovery of numerous targets such as GSTP1, Ras-association domain family 1A (RASSF1A) and retinoic acid receptor β2 (RARβ2) that become inactivated through promoter hypermethylation during the course of disease initiation and progression. This has provided the basis for translational research into methylation biomarkers for early detection and prognosis of prostate cancer. Investigations into the causes of these methylation events have yielded little definitive data. Aberrant hypomethylation and how it impacts upon prostate cancer has been less well studied. Herein we discuss the major developments in the fields of prostate cancer and DNA methylation, and how this epigenetic modification can be harnessed to address some of the key issues impeding the successful clinical management of prostate cancer.

scholarly journals DNA methylation in germ cell tumour aetiology: current understanding and outstanding questions

Reproduction ◽  
2013 ◽  
Vol 146 (2) ◽  
pp. R49-R60 ◽  
Author(s):  
Martin Cusack ◽  
Paul Scotting
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Epigenetic Modification ◽  
Germ Cell Tumour ◽  
Genome Wide ◽  
Recent Developments ◽  
Methylator Phenotype ◽  
Aberrant Dna Methylation ◽  
Promoter Region Hypermethylation

Germ cell tumours (GCTs) are a diverse group of neoplasms that can be histologically subclassified as either seminomatous or non-seminomatous. These two subtypes have distinct levels of differentiation and clinical characteristics, the non-seminomatous tumours being associated with poorer prognosis. In this article, we review how different patterns of aberrant DNA methylation relate to these subtypes. Aberrant DNA methylation is a hallmark of all human cancers, but particular subsets of cancers show unusually high frequencies of promoter region hypermethylation. Such a ‘methylator phenotype’ has been described in non-seminomatous tumours. We discuss the possible cause of distinct methylation profiles in GCTs and the potential of DNA methylation to provide new targets for therapy. We also consider how recent developments in our understanding of this epigenetic modification and the development of genome-wide technologies are shedding new light on the role of DNA methylation in cancer aetiology.

scholarly journals The role of gut microbiota in the effects of maternal obesity during pregnancy on offspring metabolism

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Liyuan Zhou ◽  
Xinhua Xiao
Keyword(s):  
Gut Microbiota ◽  
Animal Studies ◽  
Maternal Obesity ◽  
Metabolic Diseases ◽  
Microbial Colonization ◽  
Global Epidemic ◽  
Increased Risk ◽  
Colonization Hypothesis ◽  
The Impact

Obesity is considered a global epidemic. Specifically, obesity during pregnancy programs an increased risk of the offspring developing metabolic disorders in addition to the adverse effects on the mother per se. Large numbers of human and animal studies have demonstrated that the gut microbiota plays a pivotal role in obesity and metabolic diseases. Similarly, maternal obesity during pregnancy is associated with alterations in the composition and diversity of the intestine microbial community. Recently, the microbiota in the placenta, amniotic fluid, and meconium in healthy gestations has been investigated, and the results supported the “in utero colonization hypothesis” and challenged the traditional “sterile womb” that has been acknowledged worldwide for more than a century. Thus, the offspring microbiota, which is crucial for the immune and metabolic function and further health in the offspring, might be established prior to birth. As a detrimental intrauterine environment, maternal obesity influences the microbial colonization and increases the risk of metabolic diseases in offspring. This review discusses the role of the microbiota in the impact of maternal obesity during pregnancy on offspring metabolism and further analyzes related probiotic or prebiotic interventions to prevent and treat obesity and metabolic diseases.

scholarly journals Targeted systematic evolution of an RNA platform neutralizing DNMT1 function and controlling DNA methylation

2020 ◽  
Author(s):  
CL Esposito ◽  
I Autiero ◽  
MA Basal ◽  
A Sandomenico ◽  
S Ummarino ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Epigenetic Modification ◽  
Clinical Intervention ◽  
Medical Intervention ◽  
High Affinity ◽  
Cellular Assays ◽  
Systematic Evolution ◽  
Aberrant Dna Methylation ◽  
Identification And Characterization

AbstractDNA methylation is a fundamental epigenetic modification regulating gene expression. Aberrant DNA methylation is the most common molecular lesion in cancer cells. However, medical intervention has been limited to the use of toxic, unspecific demethylating drugs. Aptamers are novel high affinity targeting ligand molecules. By conjugating the inherent DNMT1 inhibiting capabilities of RNA to an aptamer platform, we generated a first-of-its kind aptamer approach that can target and neutralize DNMT1 function – the aptaDiR. Molecular modelling of RNA-DNMT1 complexes coupled with biochemical and cellular assays enabled the identification and characterization of aptaDiR. This novel RNA bio-drug blocks DNA methylation and impairs cancer cell viability.Collectively, we present an innovative RNA-based approach to modulate DNMT1 activity in cancer or diseases characterized by aberrant DNA methylation and suggest the first alternative strategy to overcome the limitations of currently approved hypomethylating protocols, which will greatly improve clinical intervention on DNA methylation.

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 Cell-Free DNA Methylation Profiling Analysis—Technologies and Bioinformatics

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1741 ◽  
Author(s):  
Huang ◽  
Wang
Keyword(s):  
Dna Methylation ◽  
Epigenetic Modification ◽  
Response To Therapy ◽  
Sequencing Data ◽  
Liquid Biopsies ◽  
Cell Free Dna ◽  
Bodily Fluids ◽  
Systemic Analysis ◽  
Free Dna ◽  
Aberrant Dna Methylation

Analysis of circulating nucleic acids in bodily fluids, referred to as “liquid biopsies”, is rapidly gaining prominence. Studies have shown that cell-free DNA (cfDNA) has great potential in characterizing tumor status and heterogeneity, as well as the response to therapy and tumor recurrence. DNA methylation is an epigenetic modification that plays an important role in a broad range of biological processes and diseases. It is well known that aberrant DNA methylation is generalizable across various samples and occurs early during the pathogenesis of cancer. Methylation patterns of cfDNA are also consistent with their originated cells or tissues. Systemic analysis of cfDNA methylation profiles has emerged as a promising approach for cancer detection and origin determination. In this review, we will summarize the technologies for DNA methylation analysis and discuss their feasibility for liquid biopsy applications. We will also provide a brief overview of the bioinformatic approaches for analysis of DNA methylation sequencing data. Overall, this review provides informative guidance for the selection of experimental and computational methods in cfDNA methylation-based studies.

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