-
Biomolecules Dec 2020Liquid biopsy based on cell-free DNA (cfDNA) enables non-invasive dynamic assessment of disease status in patients with cancer, both in the early and advanced settings.... (Review)
Review
Liquid biopsy based on cell-free DNA (cfDNA) enables non-invasive dynamic assessment of disease status in patients with cancer, both in the early and advanced settings. The analysis of DNA-methylation (DNAm) from cfDNA samples holds great promise due to the intrinsic characteristics of DNAm being more prevalent, pervasive, and cell- and tumor-type specific than genomics, for which established cfDNA assays already exist. Herein, we report on recent advances on experimental strategies for the analysis of DNAm in cfDNA samples. We describe the main steps of DNAm-based analysis workflows, including pre-analytics of cfDNA samples, DNA treatment, assays for DNAm evaluation, and methods for data analysis. We report on protocols, biomolecular techniques, and computational strategies enabling DNAm evaluation in the context of cfDNA analysis, along with practical considerations on input sample requirements and costs. We provide an overview on existing studies exploiting cell-free DNAm biomarkers for the detection and monitoring of cancer in early and advanced settings, for the evaluation of drug resistance, and for the identification of the cell-of-origin of tumors. Finally, we report on DNAm-based tests approved for clinical use and summarize their performance in the context of liquid biopsy.
Topics: Animals; Cell-Free Nucleic Acids; Computational Biology; DNA Methylation; Humans; Liquid Biopsy; Medical Oncology
PubMed: 33334040
DOI: 10.3390/biom10121677 -
Genes Nov 2023Infertility affects a significant number of couples worldwide and its incidence is increasing. While assisted reproductive technologies (ART) have revolutionized the... (Review)
Review
Infertility affects a significant number of couples worldwide and its incidence is increasing. While assisted reproductive technologies (ART) have revolutionized the treatment landscape of infertility, a significant number of couples present with an idiopathic cause for their infertility, hindering effective management. Profiling the genome and transcriptome of infertile men and women has revealed abnormal gene expression. Epigenetic modifications, which comprise dynamic processes that can transduce environmental signals into gene expression changes, may explain these findings. Indeed, aberrant DNA methylation has been widely characterized as a cause of abnormal sperm and oocyte gene expression with potentially deleterious consequences on fertilization and pregnancy outcomes. This review aims to provide a concise overview of male and female infertility through the lens of DNA methylation alterations.
Topics: Pregnancy; Male; Humans; Female; DNA Methylation; Semen; Infertility; Epigenesis, Genetic; Reproductive Techniques, Assisted
PubMed: 38136954
DOI: 10.3390/genes14122132 -
Experimental Dermatology Aug 2021The observed incidence of psoriasis has been gradually increasing over time (J Am Acad Dermatol, 03, 2009, 394), but the underlying pathogenic factors have remained... (Review)
Review
The observed incidence of psoriasis has been gradually increasing over time (J Am Acad Dermatol, 03, 2009, 394), but the underlying pathogenic factors have remained unclear. Recent studies suggest the importance of epigenetic modification in the pathogenesis of psoriasis. Aberrant epigenetic patterns including changes in DNA methylation, histone modifications and non-coding RNA expression are observed in psoriatic skin. Reversing these epigenetic mechanisms has showed improvement in psoriatic phenotypes, making epigenetic therapy a potential avenue for psoriasis treatment. Here, we summarize relevant evidence for epigenetic dysregulation contributing to psoriasis susceptibility and pathogenesis, and the factors responsible for epigenetic modifications, providing directions for potential future clinical avenues.
Topics: DNA Methylation; Epigenesis, Genetic; Histones; Humans; Psoriasis
PubMed: 33756010
DOI: 10.1111/exd.14332 -
Physiologia Plantarum Jan 2022Fleshy fruit, the most economical and nutritional value unique to flowering plants, is an important part of our daily diet. Previous studies have shown that fruit... (Review)
Review
Fleshy fruit, the most economical and nutritional value unique to flowering plants, is an important part of our daily diet. Previous studies have shown that fruit ripening is regulated by transcription factors and the plant hormone ethylene, but recent research has also shown that epigenetics also plays an essential role, especially DNA methylation. DNA methylation is the process of transferring -CH3 to the fifth carbon of cytosine residues under the action of methyltransferase to form 5-methylcytosine (5-mC). So far, most works have been focused on tomato. Tomato ripening is dynamically regulated by DNA methylation and demethylation, but the understanding of this mechanism is still in its infancy. The dysfunction of a DNA demethylase, DEMETER-like DNA demethylases 2 (DML2), prevents the ripening of tomato fruits, but immature fruits ripen prematurely under the action of DNA methylation inhibitors. Additionally, studies have shown that the relationship between fruit quality and DNA methylation is not linear, but the specific molecular mechanism is still unclear. Here, we review the recent advances in the role of DNA methylation in tomato fruit ripening, the interaction of ripening transcription factors and DNA methylation, and its effects on quality. Then, a number of questions for future research of DNA methylation regulation in tomato fruit ripening is proposed.
Topics: DNA Methylation; Ethylenes; Fruit; Gene Expression Regulation, Plant; Solanum lycopersicum; Plant Proteins
PubMed: 35040145
DOI: 10.1111/ppl.13627 -
Proceedings of the National Academy of... May 2022DNA methylation profiles have been used to develop biomarkers of aging known as epigenetic clocks, which predict chronological age with remarkable accuracy and show...
DNA methylation profiles have been used to develop biomarkers of aging known as epigenetic clocks, which predict chronological age with remarkable accuracy and show promise for inferring health status as an indicator of biological age. Epigenetic clocks were first built to monitor human aging, but their underlying principles appear to be evolutionarily conserved, as they have now been successfully developed for many mammalian species. Here, we describe reliable and highly accurate epigenetic clocks shown to apply to 93 domestic dog breeds. The methylation profiles were generated using the mammalian methylation array, which utilizes DNA sequences that are conserved across all mammalian species. Canine epigenetic clocks were constructed to estimate age and also average time to death. We also present two highly accurate human–dog dual species epigenetic clocks (R = 0.97), which may facilitate the ready translation from canine to human use (or vice versa) of antiaging treatments being developed for longevity and preventive medicine. Finally, epigenome-wide association studies here reveal individual methylation sites that may underlie the inverse relationship between breed weight and lifespan. Overall, we describe robust biomarkers to measure aging and, potentially, health status in canines.
Topics: Aging; Animals; DNA; DNA Methylation; Dogs; Epigenesis, Genetic; Epigenomics; Humans
PubMed: 35580182
DOI: 10.1073/pnas.2120887119 -
Cells Jun 2020Colorectal carcinogenesis (CRC) is caused by the gradual long-term accumulation of both genetic and epigenetic changes. Recently, epigenetic alterations have been... (Review)
Review
Colorectal carcinogenesis (CRC) is caused by the gradual long-term accumulation of both genetic and epigenetic changes. Recently, epigenetic alterations have been included in the classification of the CRC molecular subtype, and this points out their prognostic impact. As epigenetic modifications are reversible, they may represent relevant therapeutic targets. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), regulates gene expression. For many years, the deregulation of DNA methylation has been considered to play a substantial part in CRC etiology and evolution. Despite considerable advances in CRC treatment, patient therapy response persists as limited, and their profit from systemic therapies are often hampered by the introduction of chemoresistance. In addition, inter-individual changes in therapy response in CRC patients can arise from their specific (epi)genetic compositions. In this review article, we summarize the options of CRC treatment based on DNA methylation status for their predictive value. This review also includes the therapy outcomes based on the patient's methylation status in CRC patients. In addition, the current challenge of research is to develop therapeutic inhibitors of DNMT. Based on the essential role of DNA methylation in CRC development, the application of DNMT inhibitors was recently proposed for the treatment of CRC patients, especially in patients with DNA hypermethylation.
Topics: Colorectal Neoplasms; DNA Methylation; Humans
PubMed: 32599894
DOI: 10.3390/cells9061540 -
Archives of Disease in Childhood Sep 2023
Topics: Humans; Adverse Childhood Experiences; DNA Methylation
PubMed: 37591533
DOI: 10.1136/archdischild-2023-326140 -
Hormones and Behavior Feb 2020Interactions between hormones and epigenetic factors are key regulators of behaviour, but the mechanisms that underlie their effects are complex. Epigenetic factors can... (Review)
Review
Interactions between hormones and epigenetic factors are key regulators of behaviour, but the mechanisms that underlie their effects are complex. Epigenetic factors can modify sensitivity to hormones by altering hormone receptor expression, and hormones can regulate epigenetic factors by recruiting epigenetic regulators to DNA. The bidirectional nature of this relationship is becoming increasingly evident and suggests that the ability of hormones to regulate certain forms of behaviour may depend on their ability to induce changes in the epigenome. Moreover, sex differences have been reported for several epigenetic modifications, and epigenetic factors are thought to regulate sexual differentiation of behaviour, although specific mechanisms remain to be understood. Indeed, hormone-epigenome interactions are highly complex and involve both canonical and non-canonical regulatory pathways that may permit for highly specific gene regulation to promote variable forms of behavioural adaptation.
Topics: Adaptation, Physiological; Animals; Behavior; DNA Methylation; Emotional Regulation; Epigenesis, Genetic; Epigenome; Gene Expression; Histones; Hormones; Humans; Sex Characteristics
PubMed: 31927018
DOI: 10.1016/j.yhbeh.2020.104680 -
Progress in Molecular Biology and... 2023With aging, prevalence of obesity, hypertension, diabetes and renal diseases have increased globally. Over the last two decades, the prevalence of renal diseases has...
With aging, prevalence of obesity, hypertension, diabetes and renal diseases have increased globally. Over the last two decades, the prevalence of renal diseases has been intensely increasing. Renal disease and renal programming are regulated by epigenetic modifications like DNA methylation and histone modifications. Environmental factors have significant role in the pathophysiology of renal disease progression. Understanding the potential of epigenetic regulation of gene expression may be useful in renal disease prognosis, diagnosis and provides novel therapeutic measures. In a nutshell, this chapter talks about the role of epigenetic mechanisms-DNA methylation, histone modification, and noncoding RNA in different renal diseases. These include diabetic kidney disease, diabetic nephropathy, renal fibrosis, etc.
Topics: Humans; Epigenesis, Genetic; Kidney Diseases; Kidney; DNA Methylation; Aging
PubMed: 37225324
DOI: 10.1016/bs.pmbts.2023.02.013 -
Trends in Genetics : TIG Jan 2024First identified in isogenic mice, metastable epialleles (MEs) are loci where the extent of DNA methylation (DNAm) is variable between individuals but correlates across... (Review)
Review
First identified in isogenic mice, metastable epialleles (MEs) are loci where the extent of DNA methylation (DNAm) is variable between individuals but correlates across tissues derived from different germ layers within a given individual. This property, termed systemic interindividual variation (SIV), is attributed to stochastic methylation establishment before germ layer differentiation. Evidence suggests that some putative human MEs are sensitive to environmental exposures in early development. In this review we introduce key concepts pertaining to human MEs, describe methods used to identify MEs in humans, and review their genomic features. We also highlight studies linking DNAm at putative human MEs to early environmental exposures and postnatal (including disease) phenotypes.
Topics: Humans; Animals; Mice; Epigenesis, Genetic; DNA Methylation; Phenotype; Genomics; Alleles
PubMed: 38000919
DOI: 10.1016/j.tig.2023.09.007