Epigenetics Insights最新文献

Early diets in honeybees have effects on epigenome with consequences on their phenotype. Depending on the early larval diet, either royal jelly (RJ) or royal worker, 2 different female castes are generated from identical genomes, a long-lived queen with fully developed ovaries and a short-lived functionally sterile worker. To generate these prominent physiological and morphological differences between queen and worker, honeybees utilize epigenetic mechanisms which are controlled by nutritional input. These mechanisms include DNA methylation and histone post-translational modifications, mainly histone acetylation. In honeybee larvae, DNA methylation and histone acetylation may be differentially altered by RJ. This diet has biologically active ingredients with inhibitory effects on the de novo methyltransferase DNMT3A or the histone deacetylase 3 HDAC3 to create and maintain the epigenetic state necessary for developing larvae to generate a queen. DNMT and HDAC enzymes work together to induce the formation of a compacted chromatin structure, repressing transcription. Such dialog could be coordinated by their association with other epigenetic factors including the ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 (UHRF1). Through its multiple functional domains, UHRF1 acts as an epigenetic reader of both DNA methylation patterns and histone marks. The present review discusses the epigenetic regulation of honeybee's chromatin and how the early diets in honeybees can affect the DNA/histone modifying types of machinery that are necessary to stimulate the larvae to turn into either queen or worker. The review also looks at future directions in epigenetics mechanisms of honeybees, mainly the potential role of UHRF1 in these mechanisms.

Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS that affects millions of people worldwide. The causes of the disease remain unknown despite extensive efforts to understand it. CircRNAs are a unique class of endogenous non-coding RNA that are abundant, stable, conserved, and specifically expressed molecules, making them a promising biomarker of diseases. This review investigates the role of circRNA in MS pathogenicity and their potential as a biomarker through a comprehensive literature search conducted in 8 scientific databases. The studies found that there are differentially expressed circRNAs in MS patients compared to healthy controls (HC), and this difference is even more pronounced in different MS subtypes. Enrichment of circRNAs in linkage disequilibrium (LD) blocks that harbor MS-associated SNPs suggests that these SNPs manipulate the levels of circRNAs in the surrounding area, contributing to disease pathogenicity. While circRNA shows promise as an indicator or biomarker for MS disease pathology, further research is needed to fully explore its potential and impact on human biology.

Epigenetic changes may be biomarkers of health. Epigenetic age acceleration (EAA), the discrepancy between epigenetic age measured via epigenetic clocks and chronological age, is associated with morbidity and mortality. However, the intersection of epigenetic clocks with microRNAs (miRNAs) and corresponding miRNA-based health implications have not been evaluated. We analyzed DNA methylation and miRNA profiles from blood sampled among 332 individuals enrolled across 2 U.S.-based firefighter occupational studies (2015-2018 and 2018-2020). We considered 7 measures of EAA in leukocytes (PhenoAge, GrimAge, Horvath, skin-blood, and Hannum epigenetic clocks, and extrinsic and intrinsic epigenetic age acceleration). We identified miRNAs associated with EAA using individual linear regression models, adjusted for sex, race/ethnicity, chronological age, and cell type estimates, and investigated downstream effects of associated miRNAs with miRNA enrichment analyses and genomic annotations. On average, participants were 38 years old, 88% male, and 75% non-Hispanic white. We identified 183 of 798 miRNAs associated with EAA (FDR q < 0.05); 126 with PhenoAge, 59 with GrimAge, 1 with Horvath, and 1 with the skin-blood clock. Among miRNAs associated with Horvath and GrimAge, there were 61 significantly enriched disease annotations including age-related metabolic and cardiovascular conditions and several cancers. Enriched pathways included those related to proteins and protein modification. We identified miRNAs associated with EAA of multiple epigenetic clocks. PhenoAge had more associations with individual miRNAs, but GrimAge and Horvath had greater implications for miRNA-associated pathways. Understanding the relationship between these epigenetic markers could contribute to our understanding of the molecular underpinnings of aging and aging-related diseases.

Background: Epigenetics studies the impact of environmental and behavioral factors on stable phenotypic changes; however, the state of the science examining epigenomic mechanisms of regulation related to secondary health conditions (SHCs) and neuroepigenetics in chronic spinal cord injury (SCI) remain markedly underdeveloped.

Objective: This scoping review seeks to understand the state of the science in epigenetics and secondary complications following SCI.

Methods: A literature search was conducted, yielding 277 articles. The inclusion criteria were articles (1) investigating SCI and (2) examining epigenetic regulation as part of the study methodology. A total of 23 articles were selected for final inclusion.

Results: Of the 23 articles 52% focused on histone modification, while 26% focused on DNA methylation. One study had a human sample, while the majority sampled rats and mice. Primarily, studies examined regeneration, with only one study looking at clinically relevant SHC, such as neuropathic pain.

Discussion: The findings of this scoping review offer exciting insights into epigenetic and neuroepigenetic application in SCI research. Several key genes, proteins, and pathways emerged across studies, suggesting the critical role of epigenetic regulation in biological processes. This review reinforced the dearth of studies that leverage epigenetic methods to identify prognostic biomarkers in SHCs. Preclinical models of SCI were genotypically and phenotypically similar, which is not reflective of the heterogeneity found in the clinical population of persons with SCI. There is a need to develop better preclinical models and more studies that examine the role of genomics and epigenomics in understanding the diverse health outcomes associated with traumatic SCI.

Background: Alterations in DNA methylation play an important role in cancer development and progression. Dietary nutrients and lifestyle behaviors can influence DNA methylation patterns and thereby modulate cancer risk.

Introduction: To comprehensively review available evidence on how dietary and lifestyle factors impact DNA methylation and contribute to carcinogenesis through epigenetic mechanisms.

Materials and methods: A literature search was conducted using PubMed to identify relevant studies published between 2005 and 2022 that examined relationships between dietary/lifestyle factors and DNA methylation in cancer. Studies investigating the effects of dietary components (eg, micronutrients, phytochemicals), physical activity, smoking, and obesity on global and gene-specific DNA methylation changes in animal and human cancer models were included. Data on specific dietary/lifestyle exposures, cancer types, DNA methylation targets and underlying mechanisms were extracted.

Results: Multiple dietary and lifestyle factors were found to influence DNA methylation patterns through effects on DNA methyltransferase activity, methyl donor availability, and generation of oxidative stress. Altered methylation of specific genes regulating cell proliferation, apoptosis, and inflammation were linked to cancer development and progression.

Conclusion: Dietary and lifestyle interventions aimed at modulating DNA methylation have potential for both cancer prevention and treatment through epigenetic mechanisms. Further research is needed to identify actionable targets for nutrition and lifestyle-based epigenetic therapies.

Background: The global pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). About 18.4% of total Covid-19 cases were reported in children. Even though vertical transmission from mother to infant is likely to occur at a low rate, exposure to COVID-19 during fetal life may alter DNA methylation patterns with potential long-term effects.

Objective: To determine if COVID-19 infection during pregnancy alters the DNA methylation patterns in umbilical cord blood cells from term infants and to identify potential pathways and genes affected by exposure to COVID-19 infection.

Methods: Umbilical cord blood was collected from 8 infants exposed to COVID-19 during pregnancy and 8 control infants with no COVID-19 exposure. Genomic DNA was isolated from umbilical cord blood cells and genome-wide DNA methylation was performed using Illumina Methylation EPIC Array.

Results: 119 differentially methylated loci were identified at the FDR level of 0.20 (64 hypermethylated loci and 55 hypomethylated loci) in umbilical cord blood cells of COVID-19 exposed neonates compared to the control group. Important canonical pathways identified by Ingenuity Pathway Analysis (IPA) were related to stress response (corticotropin releasing hormone signaling, glucocorticoid receptor signaling, and oxytocin in brain signaling pathway), and cardiovascular disease and development (nitric oxide signaling in the cardiovascular system, apelin cardiomyocyte signaling pathways, factors promoting cardiogenesis, and renin-angiotensin signaling). The genes affected by the differential methylations were associated with cardiac, renal, hepatic, neurological diseases, developmental and immunological disorders.

Conclusions: COVID-19 induces differential DNA methylation in umbilical cord blood cells. The differentially methylated genes may contribute to hepatic, renal, cardiac, developmental and immunological disorders in offspring born to mothers with COVID-19 infection during pregnancy, and their developmental regulation.

Introduction: Exhaled breath condensate (EBC) sampling has been suggested as a less-invasive and cost-effective method to detect biological macromolecules, including miRNA. To explore the feasibility of its use as a biomarker of early effects of asbestos exposure, we conducted a preliminary test on male volunteers by comparing the miRNA profile in the EBC and the plasma using 2 different sequencing platforms.

Methods: Six male volunteers, all retired and unexposed to dust or fumes, participated in the test. RNA was extracted from 200 μL EBC samples and same-size plasma samples. Sample aliquots were processed in 2 laboratories using 2 different sequencing platforms: a MiSeq Illumina^® platform and a more performing HiSeq Illumina^® platform.

Results: The HiSeq3000^® sequencing platform identified twice as many unique molecular indexes (UMI)-validated miRNA as the MiSeq^® platform. The Spearman's correlation coefficient between EBC counts and plasma counts was significant in 5/6 subjects with either platform (MiSeq^® = 0.128-0.508, P = .026-<.001; HiSeq^® = 0.156-0.412, P = .001-<.001). The intraclass correlation coefficient confirmed the consistency of the miRNA profile over the 6 participants with both biospecimens. Exploring the agreement between the EBC and plasma samples with Bland-Altman plots showed that using the HiSeq3000^® platform substantially improved the EBC miRNA detection rate.

Conclusion: Our preliminary study confirms that, when using the HiSeq^® sequencing platform, EBC sampling is a suitable, non-invasive method to detect the miRNA profile in healthy subjects.

ALS is a fatal motor neuron disease that displays a broad variety of phenotypes ranging from early fatal courses to slowly progressing and rather benign courses. Such divergence can also be seen in genetic ALS cases with varying phenotypes bearing specific mutations, suggesting epigenetic mechanisms like DNA methylation act as disease modifiers. However, the epigenotype dictated by, in addition to other mechanisms, DNA methylation is also strongly influenced by the individual's genotype. Hence, we performed a DNA methylation study using EPIC arrays on 7 monozygotic (MZ) twin pairs discordant for ALS in whole blood, which serves as an ideal model for eliminating the effects of the genetic-epigenetic interplay to a large extent. We found one CpG site showing intra-pair hypermethylation in the affected co-twins, which maps to the Glutamate Ionotropic Receptor Kainate Type Subunit 1 gene (GRIK1). Additionally, we found 4 DMPs which were subsequently confirmed using 2 different statistical approaches. Differentially methylated regions or blocks could not be detected within the scope of this work. In conclusion, we revealed that despite a low sample size, monozygotic twin studies discordant for the disease can bring new insights into epigenetic processes in ALS, pointing to new target loci for further investigations.

Vertebrate and invertebrate models of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, have been paramount to our understanding of the pathophysiology of these conditions; however, the brain epigenetic landscape is less well established in these disease models. DNA methylation, histone modifications, and microRNAs are among commonly studied mechanisms of epigenetic regulation. Genome-wide studies and candidate studies of specific methylation marks, histone marks, and microRNAs have demonstrated the dysregulation of these mechanisms in models of neurodegenerative diseases; however, the studies to date are scarce and inconclusive and the implications of many of these changes are still not fully understood. In this review, we summarize epigenetic changes reported to date in the brain of vertebrate and invertebrate models used to study neurodegenerative diseases, specifically diseases affecting the aging population. We also discuss caveats of epigenetic research so far and the use of disease models to understand neurodegenerative diseases, with the aim of improving the use of model organisms in this context in future studies.

Background: African American women (AAW) have a high risk of both cardiometabolic (CM) illness and depressive symptoms. Depressive symptoms co-occur in individuals with CM illness at higher rates than the general population, and accelerated aging may explain this. In this secondary analysis, we examined associations between age acceleration; depressive symptoms; and CM traits (hypertension, diabetes mellitus [DM], and obesity) in a cohort of AAW.

Methods: Genomic and clinical data from the InterGEN cohort (n = 227) were used. Age acceleration was based on the Horvath method of DNA methylation (DNAm) age estimation. Accordingly, DNAm age acceleration (DNAm AA) was defined as the residuals from a linear regression of DNAm age on chronological age. Spearman's correlations, linear and logistic regression examined associations between DNAm AA, depressive symptoms, and CM traits.

Results: DNAm AA did not associate with total depressive symptom scores. DNAm AA correlated with specific symptoms including self-disgust/self-hate (-0.13, 95% CI -0.26, -0.01); difficulty with making decisions (-0.15, 95% CI -0.28, -0.02); and worry over physical health (0.15, 95% CI 0.02, 0.28), but were not statistically significant after multiple comparison correction. DNAm AA associated with obesity (0.08, 95% CI 1.02, 1.16), hypertension (0.08, 95% CI 1.01, 1.17), and DM (0.20, 95% CI 1.09, 1.40), after adjustment for potential confounders.

Conclusions: Associations between age acceleration and depressive symptoms may be highly nuanced and dependent on study design contexts. Factors other than age acceleration may explain the connection between depressive symptoms and CM traits. AAW with CM traits may be at increased risk of accelerated aging.