Epigenetics : Official Journal of the DNA Methylation Society

Transgenerational epigenetic inheritance in mammals remains a controversial phenomenon. A recent study by Takahashi et al. provides evidence for this mode of inheritance in mice by using a CRISPR/Cas9-based epigenetic editing technique to modify DNA methylation levels at specific promoters and then demonstrating the inheritance of the gain in methylation in offspring. In this technical commentary, we argue that the method used in the original study inherently amplifies the likelihood of genetic changes that thereafter lead to the heritability of epigenetic changes...

Modelling the regulatory mechanisms that determine cell fate, response to external perturbation, and disease state depends on measuring many factors, a task made more difficult by the plasticity of the epigenome. Scanning the genome for the sequence patterns defined by Position Weight Matrices (PWM) can be used to estimate transcription factor (TF) binding locations. However, this approach does not incorporate information regarding the epigenetic context necessary for TF binding. CpG methylation is an epigenetic mark influenced by environmental factors that is commonly assayed in human cohort studies...

An earlier study of ours investigating the effect of dietary lipid levels on the choline requirement of Atlantic salmon showed increasing severity of intestinal steatosis with increasing lipid levels. As choline is involved in epigenetic regulation by being the key methyl donor, pyloric caeca samples from the study were analysed for epigenetic effects of dietary lipid and choline levels. The diets varied in lipid levels between 16% and 28%, and choline levels between 1.9 and 2.3 g/kg. The diets were fed for 8 weeks to Atlantic salmon of 25 g of initial weight...

Studies suggest that clonal plants' ability to select habitats and forage in a heterogeneous environment is influenced by their past environment, with stress legacy potentially playing a crucial role. In this study, we examined parental ramets of Duchesnea indica Focke that were subject to either a control or lead-contaminated environment (past environment), and their newborn offspring were then transplanted into control, homogeneous lead or heterogeneous lead environment (present environment). We analysed how past and present environments affect plant growth and DNA methylation in offspring...

Penile squamous cell carcinoma (SCC) is a rare and aggressive tumour mainly related to lifestyle behaviour and human papillomavirus (HPV) infection. Environmentally induced loss of imprinting (LOI) at the H19 differentially methylated region (H19DMR) is associated with many cancers in the early events of tumorigenesis and may be involved in the pathogenesis of penile SCC. We sought to evaluate the DNA methylation pattern at H19DMR and its association with HPV infection in men with penile SCC by bisulfite sequencing (bis-seq)...

Physical activity is a first-line treatment for polycystic ovary syndrome (PCOS). Resistance or aerobic exercise improves metabolic complications, reproductive outcomes, and quality of life in PCOS. DNA methylation reprogramming during exercise may be the major modifier behind these changes. We sought to evaluate genome-wide DNA methylation changes after supervised resistance and aerobic exercise in women with PCOS. Exercises were performed in 56 women with PCOS (resistance, n  = 30; aerobic, n  = 26), for 16 weeks (wks), three times per week, in 50-minute to one-hour sessions...

Long noncoding RNAs (lncRNAs) regulate the progression of type 2 diabetes mellitus complicated with obstructive sleep apnoea (T2DM-OSA). However, the role of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in T2DM-OSA remains unknown. This study aimed to reveal the function of NEAT1 in T2DM-OSA and the underlying mechanism. KKAy mice were exposed to intermittent hypoxia (IH) or intermittent normoxia to generate a T2DM-OSA mouse model. HMEC-1 cells were treated with high glucose (HG) and IH to construct a T2DM-OSA cell model...

BACKGROUND: Higher early-life animal protein intake is associated with a higher childhood obesity risk compared to plant protein intake. Differential DNA methylation may represent an underlying mechanism. METHODS: We analysed associations of infant animal and plant protein intakes with DNA methylation in early (2-6 years, N  = 579) and late (7̄-12 years, N  = 604) childhood in two studies. Study-specific robust linear regression models adjusted for relevant confounders were run, and then meta-analysed using a fixed-effects model...

Currently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to hospitals for consideration of withdrawal syndrome (AWS). However, only a fraction of those admitted will experience severe AWS. Previously, we and others have shown that epigenetic indices, such as the Alcohol T-Score (ATS), can quantify recent alcohol consumption. However, whether these or other alcohol biomarkers, such as carbohydrate deficient transferrin (CDT), could identify those at risk for severe AWS is unknown...

The establishment of transgenerational effects following chemical exposure is a powerful phenomenon, capable of modulating ecosystem health beyond exposure periods. This study assessed the transgenerational effects occurring due to copper exposure in the invertebrate D. magna at the transcriptional level, while evaluating the role of exposure history on such responses. Thus, daphnids acclimated for several generations in a copper vs. clean medium were then exposed for one generation (F0) to this metal, and monitored for the following non-exposed generations (F1, F2 and F3)...

Early detection of hepatocellular carcinoma (HCC) can greatly improve the survival rate of patients. We aimed to develop a novel marker panel based on cell-free DNA (cfDNA) methylation for the detection of HCC. The differentially methylated CpG sites (DMCs) specific for HCC blood diagnosis were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, then validated by the whole genome bisulphite sequencing (WGBS) of 12 paired HCC and paracancerous tissues. The clinical performance of the panel was evaluated using tissue samples [32 HCC, chronic liver disease (CLD), and healthy individuals] and plasma cohorts (173 HCC, 199 CLD, and 98 healthy individuals)...

N6 methyladenosine (m6A), methylation at the sixth N atom of adenosine, is the most common and abundant modification in mammalian mRNAs and non-coding RNAs. Increasing evidence shows that the alteration of m6A modification level could regulate tumour proliferation, metastasis, self-renewal, and immune infiltration by regulating the related expression of tumour genes. However, the role of m6A modification in colorectal cancer (CRC) drug resistance is unclear. Here, MeRIP-seq and RNA-seq techniques were utilized to obtain mRNA, lncRNA expression, and their methylation profiles in 5-Fluorouracil (5-FU)-resistant colon cancer HCT-15 cells and control cells...

Altered epigenetic mechanisms have been previously reported in growth restricted offspring whose mothers experienced environmental insults during pregnancy in both human and rodent studies. We previously reported changes in the expression of the DNA methyltransferase Dnmt3a and the imprinted genes Cdkn1c (Cyclin-dependent kinase inhibitor 1C) and Kcnq1 (Potassium voltage-gated channel subfamily Q member 1) in the kidney tissue of growth restricted rats whose mothers had uteroplacental insufficiency induced on day 18 of gestation, at both embryonic day 20 (E20) and postnatal day 1 (PN1)...

Chronic alcohol consumption may alter mRNA methylation and expression levels of genes related to addiction and reward in the brain, potentially contributing to alcohol tolerance and dependence. Neuron-like (SH-SY5Y) and non-neuronal (SW620) cells were utilized as models to examine chronic intermittent ethanol (CIE) exposure-induced global m6A RNA methylation changes, as well as m6A mRNA methylation changes around the stop codon of three opioid receptor genes ( OPRM1 , OPRD1 , and OPRK1 ), which are known to regulate pain, reward, and addiction behaviours...

Analysis of transcription factors and chromatin modifications at the genome-wide level provides insights into gene regulatory processes, such as transcription, cell differentiation and cellular response. Chromatin immunoprecipitation is the most popular and powerful approach for mapping chromatin, and other enzyme-tethering techniques have recently become available for living cells. Among these, Cleavage Under Targets and Tagmentation (CUT&Tag) is a relatively novel chromatin profiling method that has rapidly gained popularity in the field of epigenetics since 2019...

Adverse childhood experiences (ACEs) contribute to numerous negative health outcomes across the life course and across generations. Here, we extend prior work by examining the association of maternal ACEs, and their interaction with financial stress and discrimination, with methylation status within eight differentially methylated regions (DMRs) in imprinted domains in newborns. ACEs, financial stress during pregnancy, and experience of discrimination were self-reported among 232 pregnant women. DNA methylation was assessed at PEG10 / SGCE, NNAT, IGF2, H19, PLAGL1 , PEG3 , MEG3-IG , and DLK1/MEG3 regulatory sequences using pyrosequencing...

Folate is an essential mediator in one-carbon metabolism, which provides methyl groups for DNA synthesis and methylation. The availability of active methyl groups can be influenced by the uptake of folic acid. We conducted a randomized intervention trial to test the influence of folic acid supplementation on DNA methylation in an unfortified population in Germany. A total of 16 healthy male volunteers (age range 23-61 y) were randomized to receive either 400 μg ( n  = 9) or 800 μg ( n  = 7) folic acid supplements daily for 8 weeks...

DNA methylation has been extensively utilized to study epigenetic patterns across many diseases as well as to deconvolve blood cell type proportions. This study builds upon previous studies examining methylation patterns in paediatric patients with varying stages of Crohn's disease to extend the immune profiling of these patients using a novel deconvolution approach. Compared with control subjects, we observed significantly decreased levels of CD4 memory and naive, CD8 naive, and natural killer cells and elevated neutrophil levels in Crohn's disease...

DNA methylation plays a key role in sex determination and differentiation in vertebrates. However, there are few studies on DNA methylation involved in chicken gonad development, and most focused on male hypermethylated regions (MHM). It is unclear whether there are specific differentially methylated regions (DMRs) in chicken embryonic gonads regulating sex determination and differentiation. Here, the DNA methylation maps showed that the difference of DNA methylation level between sexes was much higher at embryonic day 10 (E10) than that at embryonic day 6 (E6), and the significant differentially methylated regions at both stages were mainly distributed on the Z chromosome, including MHM1 and MHM2...

The current decline in dairy cattle fertility has resulted in significant financial losses for dairy farmers. In the past, most efforts to improve dairy cattle fertility have been focused on either management or genetics, while epigenetics have received less attention. In this study, 12 bulls were selected from a provided 100 bull list and studied (High daughter fertility = 6, Low daughter fertility = 6) for Enzymatic methylation sequencing in the Illumina HiSeq platform according to the Canadian daughter fertility index (DFI), sires with high and low daughter fertility have average DFI of 92 and 112...