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Biomolecules Jul 2019The modulation of the activity of DNA methyltransferases (DNMTs) represents a crucial epigenetic mechanism affecting gene expressions or DNA repair mechanisms in the... (Review)
Review
The modulation of the activity of DNA methyltransferases (DNMTs) represents a crucial epigenetic mechanism affecting gene expressions or DNA repair mechanisms in the cells. Aberrant modifications in the function of DNMTs are a fundamental event and part of the pathogenesis of human cancer. Phytochemicals, which are biosynthesized in plants in the form of secondary metabolites, represent an important source of biomolecules with pleiotropic effects and thus provide a wide range of possible clinical applications. It is well documented that phytochemicals demonstrate significant anticancer properties, and in this regard, rapid development within preclinical research is encouraging. Phytochemicals affect several epigenetic molecular mechanisms, including DNA methylation patterns such as the hypermethylation of tumor-suppressor genes and the global hypomethylation of oncogenes, that are specific cellular signs of cancer development and progression. This review will focus on the latest achievements in using plant-derived compounds and plant-based diets targeting epigenetic regulators and modulators of gene transcription in preclinical and clinical research in order to generate novel anticancer drugs as sensitizers for conventional therapy or compounds suitable for the chemoprevention clinical setting in at-risk individuals. In conclusion, indisputable anticancer activities of dietary phytochemicals linked with proper regulation of DNA methylation status have been described. However, precisely designed and well-controlled clinical studies are needed to confirm their beneficial epigenetic effects after long-term consumption in humans.
Topics: Antineoplastic Agents; DNA Methylation; Epigenesis, Genetic; Humans; Neoplasms; Phytochemicals
PubMed: 31323834
DOI: 10.3390/biom9070289 -
Clinical Epigenetics Dec 2021Socioeconomic position (SEP) is a major determinant of health across the life course. Yet, little is known about the biological mechanisms explaining this relationship.... (Review)
Review
BACKGROUND
Socioeconomic position (SEP) is a major determinant of health across the life course. Yet, little is known about the biological mechanisms explaining this relationship. One possibility widely pursued in the scientific literature is that SEP becomes biologically embedded through epigenetic processes such as DNA methylation (DNAm), wherein the socioeconomic environment causes no alteration in the DNA sequence but modifies gene activity in ways that shape health.
METHODS
To understand the evidence supporting a potential SEP-DNAm link, we performed a scoping review of published empirical findings on the association between SEP assessed from prenatal development to adulthood and DNAm measured across the life course, with an emphasis on exploring how the developmental timing, duration, and type of SEP exposure influenced DNAm.
RESULTS
Across the 37 identified studies, we found that: (1) SEP-related DNAm signatures varied across the timing, duration, and type of SEP indicator; (2) however, longitudinal studies examining repeated SEP and DNAm measures are generally lacking; and (3) prior studies are conceptually and methodologically diverse, limiting the interpretability of findings across studies with respect to these three SEP features.
CONCLUSIONS
Given the complex relationship between SEP and DNAm across the lifespan, these findings underscore the importance of analyzing SEP features, including timing, duration, and type. To guide future research, we highlight additional research gaps and propose four recommendations to further unravel the relationship between SEP and DNAm.
Topics: Correlation of Data; DNA Methylation; Humans; Social Class
PubMed: 34906220
DOI: 10.1186/s13148-021-01189-0 -
Journal of Translational Medicine Mar 2023Fibrosis, a process caused by excessive deposition of extracellular matrix (ECM), is a common cause and outcome of organ failure and even death. Researchers have made... (Review)
Review
Fibrosis, a process caused by excessive deposition of extracellular matrix (ECM), is a common cause and outcome of organ failure and even death. Researchers have made many efforts to understand the mechanism of fibrogenesis and to develop therapeutic strategies; yet, the outcome remains unsatisfactory. In recent years, advances in epigenetics, including chromatin remodeling, histone modification, DNA methylation, and noncoding RNA (ncRNA), have provided more insights into the fibrotic process and have suggested the possibility of novel therapy for organ fibrosis. In this review, we summarize the current research on the epigenetic mechanisms involved in organ fibrosis and their possible clinical applications.
Topics: Humans; Epigenesis, Genetic; DNA Methylation; Extracellular Matrix; Protein Processing, Post-Translational; Research Personnel
PubMed: 36864460
DOI: 10.1186/s12967-023-04018-5 -
Clinical Epigenetics Apr 2021Dysregulation of thymic stromal lymphopoietin (TSLP) expressions is linked to asthma and allergic disease. Exposure to phthalate esters, a widely used plasticizer, is...
BACKGROUND
Dysregulation of thymic stromal lymphopoietin (TSLP) expressions is linked to asthma and allergic disease. Exposure to phthalate esters, a widely used plasticizer, is associated with respiratory and allergic morbidity. Dibutyl phthalate (DBP) causes TSLP upregulation in the skin. In addition, phthalate exposure is associated with changes in environmentally induced DNA methylation, which might cause phenotypic heterogeneity. This study examined the DNA methylation of the TSLP gene to determine the potential mechanism between phthalate exposure and allergic diseases.
RESULTS
Among all evaluated, only benzyl butyl phthalate (BBzP) in the settled dusts were negatively correlated with the methylation levels of TSLP and positively associated with children's respiratory symptoms. The results revealed that every unit increase in BBzP concentration in the settled dust was associated with a 1.75% decrease in the methylation level on upstream 775 bp from the transcription start site (TSS) of TSLP (β = - 1.75, p = 0.015) after adjustment for child's sex, age, BMI, parents' smoking status, allergic history, and education levels, PM, formaldehyde, temperature; and relative humidity. Moreover, every percentage increase in the methylation level was associated with a 20% decrease in the risk of morning respiratory symptoms in the children (OR 0.80, 95% CI 0.65-0.99).
CONCLUSIONS
Exposure to BBzP in settled dust might increase children's respiratory symptoms in the morning through decreasing TSLP methylation. Therefore, the exposure to BBzP should be reduced especially for the children already having allergic diseases.
Topics: Child; Cytokines; DNA Methylation; Female; Humans; Hypersensitivity; Male; Phthalic Acids
PubMed: 33836808
DOI: 10.1186/s13148-021-01061-1 -
International Journal of Molecular... Dec 2018DNA methylation is a vital modification process in the control of genetic information, which contributes to the epigenetics by regulating gene expression without... (Review)
Review
DNA methylation is a vital modification process in the control of genetic information, which contributes to the epigenetics by regulating gene expression without changing the DNA sequence. Abnormal DNA methylation-both hypomethylation and hypermethylation-has been associated with improper gene expression, leading to several disorders. Two types of risk factors can alter the epigenetic regulation of methylation pathways: genetic factors and modifiable factors. Nutrition is one of the strongest modifiable factors, which plays a direct role in DNA methylation pathways. Large numbers of studies have investigated the effects of nutrition on DNA methylation pathways, but relatively few have focused on the biochemical mechanisms. Understanding the biological mechanisms is essential for clarifying how nutrients function in epigenetics. It is believed that nutrition affects the epigenetic regulations of DNA methylation in several possible epigenetic pathways: mainly, by altering the substrates and cofactors that are necessary for proper DNA methylation; additionally, by changing the activity of enzymes regulating the one-carbon cycle; and, lastly, through there being an epigenetic role in several possible mechanisms related to DNA demethylation activity. The aim of this article is to review the potential underlying biochemical mechanisms that are related to diet modifications in DNA methylation and demethylation.
Topics: Animals; Carbon Cycle; DNA Methylation; DNA-Cytosine Methylases; Diet; Epigenesis, Genetic; Gene Expression Regulation; Humans
PubMed: 30558203
DOI: 10.3390/ijms19124055 -
Cells Dec 2022DNA methylation, histone posttranslational modifications, higher-order chromatin organization and regulation by noncoding RNAs are considered as the basic mechanisms...
DNA methylation, histone posttranslational modifications, higher-order chromatin organization and regulation by noncoding RNAs are considered as the basic mechanisms underlying the epigenetic memory [...].
Topics: Histones; Epigenesis, Genetic; DNA Methylation; Histone Code; Protein Processing, Post-Translational
PubMed: 36611903
DOI: 10.3390/cells12010109 -
Genes Jan 2022Epigenetic changes have been identified as a major driver of fundamental metabolic pathways. More specifically, the importance of epigenetic regulatory mechanisms for... (Review)
Review
Epigenetic changes have been identified as a major driver of fundamental metabolic pathways. More specifically, the importance of epigenetic regulatory mechanisms for biological processes like speciation and embryogenesis has been well documented and revealed the direct link between epigenetic modifications and various diseases. In this review, we focus on epigenetic changes in animals with special attention on human DNA methylation utilizing ancient and modern genomes. Acknowledging the latest developments in ancient DNA research, we further discuss paleoepigenomic approaches as the only means to infer epigenetic changes in the past. Investigating genome-wide methylation patterns of ancient humans may ultimately yield in a more comprehensive understanding of how our ancestors have adapted to the changing environment, and modified their lifestyles accordingly. We discuss the difficulties of working with ancient DNA in particular utilizing paleoepigenomic approaches, and assess new paleoepigenomic data, which might be helpful in future studies.
Topics: Animals; DNA Methylation; DNA, Ancient; Epigenesis, Genetic; Epigenomics; Genome
PubMed: 35205223
DOI: 10.3390/genes13020178 -
The New Phytologist Sep 2022The impact of epigenetic modifications on the efficacy of CRISPR/Cas9-mediated double-stranded DNA breaks and subsequent DNA repair is poorly understood, especially in...
The impact of epigenetic modifications on the efficacy of CRISPR/Cas9-mediated double-stranded DNA breaks and subsequent DNA repair is poorly understood, especially in plants. In this study, we investigated the effect of the level of cytosine methylation on the outcome of CRISPR/Cas9-induced mutations at multiple Cas9 target sites in Nicotiana benthamiana leaf cells using next-generation sequencing. We found that high levels of promoter methylation, but not gene-body methylation, decreased the frequency of Cas9-mediated mutations. DNA methylation also influenced the ratio of insertions and deletions and potentially the type of Cas9 cleavage in a target-specific manner. In addition, we detected an over-representation of deletion events governed by a single 5'-terminal nucleotide at Cas9-induced DNA breaks. Our findings suggest that DNA methylation can indirectly impair Cas9 activity and subsequent DNA repair, probably through changes in the local chromatin structure. In addition to the well described Cas9-induced blunt-end double-stranded DNA breaks, we provide evidence for Cas9-mediated staggered DNA cuts in plant cells. Both types of cut may direct microhomology-mediated DNA repair by a novel, as yet undescribed, mechanism.
Topics: CRISPR-Cas Systems; DNA Breaks, Double-Stranded; DNA End-Joining Repair; DNA Methylation; DNA Repair; Gene Editing; Mutation
PubMed: 35524464
DOI: 10.1111/nph.18212 -
BioMed Research International 2015The epigenome consists of chemical changes in DNA and chromatin that without modifying the DNA sequence modulate gene expression and cellular phenotype. The epigenome is... (Review)
Review
The epigenome consists of chemical changes in DNA and chromatin that without modifying the DNA sequence modulate gene expression and cellular phenotype. The epigenome is highly plastic and reacts to changing external conditions with modifications that can be inherited to daughter cells and across generations. Whereas this innate plasticity allows for adaptation to a changing environment, it also implies the potential of epigenetic derailment leading to so-called epimutations. DNA methylation is the most studied epigenetic mark. DNA methylation changes have been associated with cancer, infertility, cardiovascular, respiratory, metabolic, immunologic, and neurodegenerative pathologies. Experiments in rodents demonstrate that exposure to a variety of chemical stressors, occurring during the prenatal or the adult life, may induce DNA methylation changes in germ cells, which may be transmitted across generations with phenotypic consequences. An increasing number of human biomonitoring studies show environmentally related DNA methylation changes mainly in blood leukocytes, whereas very few data have been so far collected on possible epigenetic changes induced in the germline, even by the analysis of easily accessible sperm. In this paper, we review the state of the art on factors impinging on DNA methylation in the germline, highlight gaps of knowledge, and propose priorities for future studies.
Topics: DNA Methylation; Environment; Epigenesis, Genetic; Gene-Environment Interaction; Germ Cells; Humans; Male; Mutation; Spermatozoa
PubMed: 26339587
DOI: 10.1155/2015/123484 -
Genes Sep 2023With the development of urban industrialization, the increasing ozone concentration (O) at ground level stresses on the survival of plants. Plants have to adapt to ozone...
With the development of urban industrialization, the increasing ozone concentration (O) at ground level stresses on the survival of plants. Plants have to adapt to ozone stress. DNA methylation is crucial for a rapid response to abiotic stress in plants. Little information is known regarding the epigenetic response of DNA methylation of plants to O stress. This study is designed to explore the epigenetic mechanism and identify a possible core modification of DNA methylation or genes in the plant, in response to O stress. We investigated the agronomic traits and genome-wide DNA methylation variations of the Japonica rice cultivar Nipponbare in response to O stress at three high concentrations (80, 160, and 200 nmol·mol), simulated using open-top chambers (OTC). The flag leaf length, panicle length, and hundred-grain weight of rice showed beneficial effects at 80 nmol·mol O and an inhibitory effect at both 160 and 200 nmol·mol O The methylation-sensitive amplified polymorphism results showed that the O-induced genome-wide methylation alterations account for 14.72-15.18% at three different concentrations. Our results demonstrated that methylation and demethylation alteration sites were activated throughout the O stress, mainly at CNG sites. By recovering and sequencing bands with methylation alteration, ten stress-related differentially amplified sequences, widely present on different chromosomes, were obtained. Our findings show that DNA methylation may be an active and rapid epigenetic response to ozone stress. These results can provide us with a theoretical basis and a reference to look for more hereditary information about the molecular mechanism of plant resistance to O pollution.
Topics: DNA Methylation; Oryza; Ozone; Epigenesis, Genetic; Mutation
PubMed: 37895237
DOI: 10.3390/genes14101888