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European Journal of Internal Medicine Aug 2023Epigenetics is a rapidly growing field of biology that studies the changes in gene expression that are not due to alterations in the DNA sequence but rather the chemical... (Review)
Review
Epigenetics is a rapidly growing field of biology that studies the changes in gene expression that are not due to alterations in the DNA sequence but rather the chemical modifications of DNA and its associated proteins. Epigenetic mechanisms can profoundly influence gene expression, cell differentiation, tissue development, and disease susceptibility. Understanding epigenetic changes is essential to elucidate the mechanisms underlying the increasingly recognized role of environmental and lifestyle factors in health and disease and the intergenerational transmission of phenotypes. Recent studies suggest epigenetics may be critical in various diseases, from cardiovascular disease and cancer to neurodevelopmental and neurodegenerative disorders. Epigenetic modifications are potentially reversible and could provide new therapeutic avenues for treating these diseases using epigenetic modulators. Moreover, epigenetics provide insight into disease pathogenesis and biomarkers for disease diagnosis and risk stratification. Nevertheless, epigenetic interventions have the potential for unintended consequences and may potentially lead to increased risks of unexpected outcomes, such as adverse drug reactions, developmental abnormalities, and cancer. Therefore, rigorous studies are essential to minimize the risks associated with epigenetic therapies and to develop safe and effective interventions for improving human health. This article provides a synthetic and historical view of the origin of epigenetics and some of the most relevant achievements.
Topics: Humans; DNA Methylation; Epigenesis, Genetic; Neoplasms
PubMed: 37277249
DOI: 10.1016/j.ejim.2023.05.036 -
Cell Stem Cell Dec 2023Studies of mammalian development have advanced our understanding of the genetic, epigenetic, and cellular processes that orchestrate embryogenesis and have uncovered new... (Review)
Review
Studies of mammalian development have advanced our understanding of the genetic, epigenetic, and cellular processes that orchestrate embryogenesis and have uncovered new insights into the unique aspects of human embryogenesis. Recent studies have now produced the first epigenetic maps of early human embryogenesis, stimulating new ideas about epigenetic reprogramming, cell fate control, and the potential mechanisms underpinning developmental plasticity in human embryos. In this review, we discuss these new insights into the epigenetic regulation of early human development and the importance of these processes for safeguarding development. We also highlight unanswered questions and key challenges that remain to be addressed.
Topics: Humans; DNA Methylation; Embryo, Mammalian; Embryonic Development; Epigenesis, Genetic
PubMed: 37858333
DOI: 10.1016/j.stem.2023.09.010 -
Nature Communications Jun 2023High-throughput tests for early cancer detection can revolutionize public health and reduce cancer morbidity and mortality. Here we show a DNA methylation signature for...
High-throughput tests for early cancer detection can revolutionize public health and reduce cancer morbidity and mortality. Here we show a DNA methylation signature for hepatocellular carcinoma (HCC) detection in liquid biopsies, distinct from normal tissues and blood profiles. We developed a classifier using four CpG sites, validated in TCGA HCC data. A single F12 gene CpG site effectively differentiates HCC samples from other blood samples, normal tissues, and non-HCC tumors in TCGA and GEO data repositories. The markers were validated in a separate plasma sample dataset from HCC patients and controls. We designed a high-throughput assay using next-generation sequencing and multiplexing techniques, analyzing plasma samples from 554 clinical study participants, including HCC patients, non-HCC cancers, chronic hepatitis B, and healthy controls. HCC detection sensitivity was 84.5% at 95% specificity and 0.94 AUC. Implementing this assay for high-risk individuals could significantly decrease HCC morbidity and mortality.
Topics: Carcinoma, Hepatocellular; Liver Neoplasms; Liver; DNA Methylation; Humans
PubMed: 37286539
DOI: 10.1038/s41467-023-39055-7 -
Ageing Research Reviews Jul 2023Epigenetic aging clocks have gained significant attention as a tool for predicting age-related health conditions in clinical and research settings. They have enabled... (Review)
Review
Epigenetic aging clocks have gained significant attention as a tool for predicting age-related health conditions in clinical and research settings. They have enabled geroscientists to study the underlying mechanisms of aging and assess the effectiveness of anti-aging therapies, including diet, exercise and environmental exposures. This review explores the effects of modifiable lifestyle factors' on the global DNA methylation landscape, as seen by aging clocks. We also discuss the underlying mechanisms through which these factors contribute to biological aging and provide comments on what these findings mean for people willing to build an evidence-based pro-longevity lifestyle.
Topics: Humans; Epigenesis, Genetic; Aging; Longevity; DNA Methylation; Diet
PubMed: 37211319
DOI: 10.1016/j.arr.2023.101956 -
Nature Cell Biology Oct 2023Germline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for...
Germline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from human embryonic stem cells in vitro. We show that switching from BMP signalling for PGC specification to Activin A and retinoic acid resulted in DMRT1 and CDH5 expression, the indicators of migratory PGCs in vivo. Moreover, the induction of DMRT1 and SOX17 in PGC-like cells promoted epigenetic resetting with striking global enrichment of 5-hydroxymethylcytosine and locus-specific loss of 5-methylcytosine at DMRT1 binding sites and the expression of DAZL representing DNA methylation-sensitive genes, a hallmark of the germline commitment programme. We provide insight into the unique role of DMRT1 in germline development for advances in human germ cell biology and in vitro gametogenesis.
Topics: Humans; Cell Differentiation; DNA Methylation; Germ Cells; Human Embryonic Stem Cells; Signal Transduction
PubMed: 37709822
DOI: 10.1038/s41556-023-01224-7 -
Hypertension (Dallas, Tex. : 1979) Aug 2023
Topics: DNA Methylation; Epigenesis, Genetic; Epigenomics; Humans
PubMed: 37470774
DOI: 10.1161/HYPERTENSIONAHA.123.21197 -
Epigenetics Dec 2023DNA methylation, one of the best characterized epigenetic marks in the human genome, plays a pivotal role in gene transcription regulation and other biological processes...
DNA methylation, one of the best characterized epigenetic marks in the human genome, plays a pivotal role in gene transcription regulation and other biological processes in humans. On top of that, the DNA methylome undergoes profound changes in cancer and other disorders. However, large-scale and population-based studies are limited by high costs and the need for considerable expertise in data analysis for whole-genome bisulphite-sequencing methodologies. Following the success of the EPIC DNA methylation microarray, the newly developed Infinium HumanMethylationEPIC version 2.0 (900K EPIC v2) is now available. This new array contains more than 900,000 CpG probes covering the human genome and excluding masked probes from the previous version. The 900K EPIC v2 microarray adds more than 200,000 probes covering extra DNA cis-regulatory regions such as enhancers, super-enhancers and CTCF binding regions. Herein, we have technically and biologically validated the new methylation array to show its high reproducibility and consistency among technical replicates and with DNA extracted from FFPE tissue. In addition, we have hybridized primary normal and tumoural tissues and cancer cell lines from different sources and tested the robustness of the 900K EPIC v2 microarray when analysing the different DNA methylation profiles. The validation highlights the improvements offered by the new array and demonstrates the versatility of this updated tool for characterizing the DNA methylome in human health and disease.
Topics: Humans; DNA Methylation; Epigenome; Reproducibility of Results; Microarray Analysis; Cell Line
PubMed: 36871255
DOI: 10.1080/15592294.2023.2185742 -
Gut Microbes Dec 2023Individuals with nonalcoholic fatty liver disease (NAFLD) have an altered gut microbiota composition. Moreover, hepatic DNA methylation may be altered in the state of...
Individuals with nonalcoholic fatty liver disease (NAFLD) have an altered gut microbiota composition. Moreover, hepatic DNA methylation may be altered in the state of NAFLD. Using a fecal microbiota transplantation (FMT) intervention, we aimed to investigate whether a change in gut microbiota composition relates to altered liver DNA methylation in NAFLD. Moreover, we assessed whether plasma metabolite profiles altered by FMT relate to changes in liver DNA methylation. Twenty-one individuals with NAFLD underwent three 8-weekly vegan allogenic donor ( = 10) or autologous ( = 11) FMTs. We obtained hepatic DNA methylation profiles from paired liver biopsies of study participants before and after FMTs. We applied a multi-omics machine learning approach to identify changes in the gut microbiome, peripheral blood metabolome and liver DNA methylome, and analyzed cross-omics correlations. Vegan allogenic donor FMT compared to autologous FMT induced distinct differential changes in I) gut microbiota profiles, including increased abundance of and potential probiotic ; II) plasma metabolites, including altered levels of phenylacetylcarnitine (PAC) and phenylacetylglutamine (PAG) both from gut-derived phenylacetic acid, and of several choline-derived long-chain acylcholines; and III) hepatic DNA methylation profiles, most importantly in Threonyl-TRNA Synthetase 1 ( and Zinc finger protein 57 (. Multi-omics analysis showed that and __170 positively correlated with both PAC and PAG. negatively correlated with DNA methylation of cg16885113 in . Alterations in gut microbiota composition by FMT caused widespread changes in plasma metabolites (e.g. PAC, PAG, and choline-derived metabolites) and liver DNA methylation profiles in individuals with NAFLD. These results indicate that FMTs might induce metaorganismal pathway changes, from the gut bacteria to the liver.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Fecal Microbiota Transplantation; DNA Methylation; Multiomics; Gastrointestinal Microbiome; Choline
PubMed: 37317027
DOI: 10.1080/19490976.2023.2223330 -
The Journal of Allergy and Clinical... Nov 2023Human epigenetic variation is associated with both environmental exposures and allergic diseases and can potentially serve as a biomarker connecting climate change with... (Review)
Review
Human epigenetic variation is associated with both environmental exposures and allergic diseases and can potentially serve as a biomarker connecting climate change with allergy and airway diseases. In this narrative review, we summarize recent human epigenetic studies examining exposure to temperature, precipitation, extreme weather events, and malnutrition to discuss findings as they relate to allergic and airway diseases. Temperature has been the most widely studied exposure, with the studies implicating both short-term and long-term exposures with epigenetic alterations and epigenetic aging. Few studies have examined natural disasters or extreme weather events. The studies available have reported differential DNA methylation of multiple genes and pathways, some of which were previously associated with asthma or allergy. Few studies have integrated climate-related events, epigenetic biomarkers, and allergic disease together. Prospective longitudinal studies are needed along with the collection of target tissues beyond blood samples, such as nasal and skin cells. Finally, global collaboration to increase diverse representation of study participants, particularly those most affected by climate injustice, as well as strengthen replication, validation, and harmonization of measurements will be needed to elucidate the impacts of climate change on the human epigenome.
Topics: Humans; Climate Change; Prospective Studies; Hypersensitivity; Biomarkers; DNA Methylation; Respiration Disorders; Epigenesis, Genetic
PubMed: 37741554
DOI: 10.1016/j.jaci.2023.09.011