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The influence of sex and heredity on DNA methylation in the somatic tissues of mice has been well-documented, with similar hereditary effects reported in honeybees. However, the extent to which these factors affect DNA methylation in molluscan somatic tissues remains poorly understood. In this study, we investigated genomic DNA methylation patterns in the adductor muscle of two genetically distinct oyster strains using whole-genome bisulfite sequencing (WGBS). Our analysis identified significant differences in DNA methylation between sexes, with females exhibiting a global reduction compared to males. Furthermore, approximately half of the differentially methylated sites between the two parental strains were conserved in their offspring. Regions with differential methylation in parents typically exhibited intermediate methylation levels in the F1 progeny, whereas consistently methylated regions in parents maintained similar methylation levels in their progeny. These findings suggest that offspring DNA methylation is strongly influenced by parental methylation profiles, highlighting its potential role in sexual determination in oysters., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The autonomous and active Long-Interspersed Element-1 (LINE-1, L1) and the non-autonomous Alu retrotransposon elements, contributing to 30% of the human genome, are the most abundant repeated sequences. With more than 90% of their sequences being methylated in normal cells, these elements undeniably contribute to the global DNA methylation level and constitute a major part of circulating-cell-free DNA (cfDNA). So far, the hypomethylation status of LINE-1 and Alu in cellular and extracellular DNA has long been considered a prevailing hallmark of ageing-related diseases and cancer. This study demonstrated that errors in LINE-1 and Alu methylation level measurements were caused by an excessive input quantity of genomic DNA used for bisulfite conversion. Using the minuscule DNA amount of 0.5 ng, much less than what has been used and recommended so far (500 ng-2 μg) or 1 μL of cfDNA extracted from 1 mL of blood, we revealed hypermethylation of LINE-1 and Alu in 407 tumour samples of primary breast, colon and lung cancers when compared with the corresponding pair-matched adjacent normal tissue samples (P < 0.05–0.001), and in cfDNA from 296 samples of lung cancers as compared with 477 samples from healthy controls (P < 0.0001). More importantly, LINE-1 hypermethylation in cfDNA is associated with healthy ageing. Our results have not only contributed to the standardized bisulfite-based protocols for DNA methylation assays, particularly in applications on repeated sequences but also provided another perspective for other repetitive sequences whose epigenetic properties may have crucial impacts on genome architecture and human health. [ABSTRACT FROM AUTHOR]

The resistance of colorectal cancer (CRC) to conventional therapeutic modalities, such as radiation therapy and chemotherapy, along with the associated side effects, significantly limits effective anticancer strategies. Numerous epigenetic investigations have unveiled that naturally occurring stilbenes can modify or reverse abnormal epigenetic alterations, particularly aberrant DNA methylation status, offering potential avenues for preventing or treating CRC. By modulating the activity of the DNA methylation machinery components, phytochemicals may influence the various stages of CRC carcinogenesis through multiple molecular mechanisms. Several epigenetic studies, especially preclinical research, have highlighted the effective DNA methylation modulatory effects of stilbenes with minimal adverse effects on organisms, particularly in combination therapies for CRC. However, the available preclinical and clinical data regarding the effects of commonly encountered stilbenes against CRC are currently limited. Therefore, additional epigenetic research is warranted to explore the preventive potential of these phytochemicals in CRC development and to validate their therapeutic application in the prevention and treatment of CRC. This review aims to provide an overview of selected bioactive stilbenes as potential chemopreventive agents for CRC with a focus on their modulatory mechanisms of action, especially in targeting alterations in DNA methylation machinery in CRC. [ABSTRACT FROM AUTHOR]

Hypertension, a multifaceted cardiovascular disorder influenced by genetic, epigenetic, and environmental factors, poses a significant risk for the development of coronary artery disease (CAD) in individuals with type 2 diabetes mellitus (T2DM). Epigenetic alterations, particularly in histone modifications, DNA methylation, and microRNAs, play a pivotal role in unraveling the complex molecular underpinnings of blood pressure regulation. This review emphasizes the crucial interplay between epigenetic attributes and hypertension, shedding light on the prominence of DNA methylation, both globally and at the gene-specific level, in essential hypertension. Additionally, histone modifications, including acetylation and methylation, emerge as essential epigenetic markers linked to hypertension. Furthermore, microRNAs exert regulatory influence on blood pressure homeostasis, targeting key genes within the aldosterone and renin-angiotensin pathways. Understanding the intricate crosstalk between genetics and epigenetics in hypertension is particularly pertinent in the context of its interaction with T2DM, where hypertension serves as a notable risk factor for the development of CAD. These findings not only contribute to the comprehensive elucidation of essential hypertension but also offer promising avenues for innovative strategies in the prevention and treatment of cardiovascular complications, especially in the context of T2DM. [ABSTRACT FROM AUTHOR]

The epigenome—the chemical modifications and chromatin-related packaging of the genome—enables the same genetic template to be activated or repressed in different cellular settings. This multi-layered mechanism facilitates cell-type specific function by setting the local sequence and 3D interactive activity level. Gene transcription is further modulated through the interplay with transcription factors and co-regulators. The human body requires this epigenomic apparatus to be precisely installed throughout development and then adequately maintained during the lifespan. The causal role of the epigenome in human pathology, beyond imprinting disorders and specific tumour suppressor genes, was further brought into the spotlight by large-scale sequencing projects identifying that mutations in epigenomic machinery genes could be critical drivers in both cancer and developmental disorders. Abrogation of this cellular mechanism is providing new molecular insights into pathogenesis. However, deciphering the full breadth and implications of these epigenomic changes remains challenging. Knowledge is accruing regarding disease mechanisms and clinical biomarkers, through pathogenically relevant and surrogate tissue analyses, respectively. Advances include consortia generated cell-type specific reference epigenomes, high-throughput DNA methylome association studies, as well as insights into ageing-related diseases from biological ‘clocks’ constructed by machine learning algorithms. Also, 3rd-generation sequencing is beginning to disentangle the complexity of genetic and DNA modification haplotypes. Cell-free DNA methylation as a cancer biomarker has clear clinical utility and further potential to assess organ damage across many disorders. Finally, molecular understanding of disease aetiology brings with it the opportunity for exact therapeutic alteration of the epigenome through CRISPR-activation or inhibition. [ABSTRACT FROM AUTHOR]

Background: Vitamin C (vitC) enhances the activity of 2-oxoglutarate-dependent dioxygenases, including TET enzymes, which catalyse DNA demethylation, and Jumonji-domain histone demethylases. The epigenetic remodelling promoted by vitC improves the efficiency of induced pluripotent stem cell derivation, and is required to attain a ground-state of pluripotency in embryonic stem cells (ESCs) that closely mimics the inner cell mass of the early blastocyst. However, genome-wide DNA and histone demethylation can lead to upregulation of transposable elements (TEs), and it is not known how vitC addition in culture media affects TE expression in pluripotent stem cells. Results: Here we show that vitC increases the expression of several TE families, including evolutionarily young LINE-1 (L1) elements, in mouse ESCs. We find that TET activity is dispensable for L1 upregulation, and that instead it occurs largely as a result of H3K9me3 loss mediated by KDM4A/C histone demethylases. Despite increased L1 levels, we did not detect increased somatic insertion rates in vitC-treated cells. Notably, treatment of human ESCs with vitC also increases L1 protein levels, albeit through a distinct, post-transcriptional mechanism. Conclusion: VitC directly modulates the expression of mouse L1s and other TEs through epigenetic mechanisms, with potential for downstream effects related to the multiple emerging roles of L1s in cellular function. [ABSTRACT FROM AUTHOR]

The biology of fish sperm, an important topic in the research of reproduction and fisheries from basic science to evolutionary and applied aspects, has implications for aquaculture management, fish breeding and biological conservation. The quality of spermatozoa plays a vital role in fish fertility, and directly affects the health and performance of offspring. Environmental factors that affect determinants of spermatozoa quality usually reflected in the DNA methylation pattern of the spermatozoa epigenome, which may change offspring's performance. The aim of the present study was to conduct a review on existing data about DNA methylation in fish spermatozoa as a biological tool for identifying the quality of offspring based on their phenotypes and performances. Furthermore, this study provides valuable knowledge from fundamental to applied sciences dealing with enhancement of breeding selection, fish reproduction and environmental adaptation. The review also describes the individual parts related to DNA methylation in fish, including overview of the methods which can be used to study DNA methylation, DNA methylation dynamics and epigenetic inheritance; identification of DNA methylation changes in sperm function in response to internal and external environment constraints, and potential relationships between DNA methylation and physiological regulation of spermatozoa quality determinants. Overall, the present study revealed that our knowledge about intergenerational inheritance of the performance and adaptability of fish through sperm DNA methylation is very limited, and no general conclusion could be approached from literature mostly due to non‐standardized experimental protocol or analytical tools. [ABSTRACT FROM AUTHOR]

Reduced insulin-like growth factor 2 (IGF2) levels in Alzheimer's disease (AD) may be the mechanism relating age-related metabolic disorders to dementia. Since Igf2 is an imprinted gene, we examined age and sex differences in the relationship between amyloid-beta 1–42 (Aβ42) accumulation and epigenetic regulation of the Igf2/H19 gene cluster in cerebrum, liver, and plasma of young and old male and female 5xFAD mice, in frontal cortex of male and female AD and non-AD patients, and in HEK293 cell cultures. We show IGF2 levels, Igf2 expression, histone acetylation, and H19 ICR methylation are lower in females than males. However, elevated Aβ42 levels are associated with Aβ42 binding to Igf2 DMR2, increased DNA and histone methylation, and a reduction in Igf2 expression and IGF2 levels in 5xFAD mice and AD patients, independent of H19 ICR methylation. Cell culture results confirmed the binding of Aβ42 to Igf2 DMR2 increased DNA and histone methylation, and reduced Igf2 expression. These results indicate an age- and sex-related causal relationship among Aβ42 levels, epigenomic state, and Igf2 expression in AD and provide a potential mechanism for Igf2 regulation in normal and pathological conditions, suggesting IGF2 levels may be a useful diagnostic biomarker for Aβ42 targeted AD therapies. [ABSTRACT FROM AUTHOR]

Given the global increase in air pollution and its crucial role in human health, as well as the steep rise in prevalence of metabolic syndrome (MetS), a better understanding of the underlying mechanisms by which environmental pollution may influence MetS is imperative. Exposure to air pollution is known to impact DNA methylation, which in turn may affect human health. This paper comprehensively reviews the evidence for the hypothesis that the effect of air pollution on the MetS is mediated by DNA methylation in blood. First, we present a summary of the impact of air pollution on metabolic dysregulation, including the components of MetS, i.e., disorders in blood glucose, lipid profile, blood pressure, and obesity. Then, we provide evidence on the relation between air pollution and endothelial dysfunction as one possible mechanism underlying the relation between air pollution and MetS. Subsequently, we review the evidence that air pollution (PM, ozone, NO2 and PAHs) influences DNA methylation. Finally, we summarize association studies between DNA methylation and MetS. Integration of current evidence supports our hypothesis that methylation may partly mediate the effect of air pollution on MetS. [ABSTRACT FROM AUTHOR]

Epigenetic mechanisms, such as DNA methylation, regulate gene expression and play a role in the development of insulin resistance. This study evaluates how the BMI z-score (BMIz) and the homeostatic model assessment of insulin resistance (HOMA-IR), alone or in combination, relate to clinical outcomes and DNA methylation patterns in prepubertal children. DNA methylation in peripheral blood mononuclear cells (PBMCs) and clinical outcomes were measured in a cohort of 41 prepubertal children. Children with higher HOMA-IR had higher blood pressure and plasma lactate levels while children with higher BMIz had higher triglycerides levels. Moreover, the DNA methylation analysis demonstrated that a 1 unit increase in the BMIz was associated with a 0.41 (95% CI: 0.29, 0.53) increase in methylation of a CpG near the PPP6R2 gene. This gene is important in the regulation of NF-kB expression. However, there was no strong evidence that the BMIz and the HOMA-IR were synergistically related to any clinical or DNA methylation outcomes. In summary, the results suggest that obesity and insulin resistance may impact metabolic health both independently in prepubertal children. In addition, obesity also has an impact on the DNA methylation of the PPP6R2 gene. This may be a novel underlying starting point for the systemic inflammation associated with obesity and insulin resistance, in this population. [ABSTRACT FROM AUTHOR]

Neuromedin U (NMU) is a neuropeptide involved in gut-brain axis, energy balance and immune response. We aimed at analysing the association between NMU epigenetic variability and metabolic indices and the potential mediating role of low-grade inflammation in a general population of Italian adults. NMU Blood DNA methylation levels at two CpG islands (NMU76 and NMU32) were analysed using pyrosequencing in a randomly selected sub-cohort of 1,160 subjects from the Moli-sani study (≥35years; 49.20% men). Multivariable regressions adjusted for age, sex, smoking, alcohol and vegetable consumption were performed to estimate the associations between methylation and metabolic phenotypes (BMI, waist-to-hip ratio, blood pressure, glucose, HOMA-IR, lipids, lipoprotein(a) and apolipoproteins). Mediation analysis was performed to identify the influence of low-grade inflammation in the association using a composite index based on C reactive protein, granulocyte-to-lymphocyte ratio (GLR), platelet and white blood cell counts (INFLA-score). Using principal component analysis four methylation factors were identified: NMU76-F1, NMU76-F2, NMU32-F1 and NMU32-F2. NMU76-F1 was FDR significantly associated with total cholesterol (for 1 SD increase: β = 4.5 ± 1.4 mg/dL of, R2 = 10.8%, p = 0.001), ApoB (0.03 ± 0.01 g/L, 12.2%, p = 0.0004), with INFLA-score (1.05 ± 0.22, p = 2.7E-6) and GLR (-0.27 ± 0.03, 30.4%, p = 1.3E-20). GLR and lymphocyte numbers mediate the association of NMU76-F1 with cholesterol (24.0% of total effect, Sobel p = 0.013) and ApoB (42.6%, p = 9E-7), respectively. These findings suggest that NMU promoter methylation patterns could mark a pathway linking lipids with haematopoiesis and systemic inflammation. [ABSTRACT FROM AUTHOR]

Haplo-diploidy and the relatedness asymmetries it generates mean that social insects are prime candidates for the evolution of genomic imprinting. In single-mating social insect species, some genes may be selected to evolve genomic mechanisms that enhance reproduction by workers when they are inherited from a female. This situation reverses in multiple mating species, where genes inherited from fathers can be under selection to enhance the reproductive success of daughters. Reciprocal crosses between subspecies of honeybees have shown strong parent-of-origin effects on worker reproductive phenotypes, and this could be evidence of such genomic imprinting affecting genes related to worker reproduction. It is also possible that social insect fathers directly affect gene expression in their daughters, for example, by placing small interfering RNA molecules in semen. Gene expression studies have repeatedly found evidence of parent-specific gene expression in social insects, but it is unclear at this time whether this arises from genomic imprinting, paternal manipulation, an artefact of cyto-nuclear interactions, or all of these. This article is part of the theme issue 'How does epigenetics influence the course of evolution?' [ABSTRACT FROM AUTHOR]

Objective: To identify methylation quantitative trait loci (mQTLs) correlating with osteoarthritis (OA) risk alleles and to undertake mechanistic characterization as a means of target gene prioritization. Methods: We used genome‐wide genotyping and cartilage DNA methylation array data in a discovery screen of novel OA risk loci. This was followed by methylation, gene expression analysis, and genotyping studies in additional cartilage samples, accompanied by in silico analyses. Results: We identified 4 novel OA mQTLs. The most significant mQTL contained 9 CpG sites where methylation correlated with OA risk genotype, with 5 of the CpG sites having P values <1 × 10−10. The 9 CpG sites reside in an interval of only 7.7 kb within the PLEC gene and form 2 distinct clusters. We were able to prioritize PLEC and the adjacent gene GRINA as independent targets of the OA risk. We identified PLEC and GRINA expression QTLs operating in cartilage, as well as methylation‐expression QTLs operating on the 2 genes. GRINA and PLEC also demonstrated differential expression between OA hip and non‐OA hip cartilage. Conclusion: PLEC encodes plectin, a cytoskeletal protein that maintains tissue integrity by regulating intracellular signaling in response to mechanical stimuli. GRINA encodes the ionotropic glutamate receptor TMBIM3 (transmembrane BAX inhibitor 1 motif–containing protein family member 3), which regulates cell survival. Based on our results, we hypothesize that in a joint predisposed to OA, expression of these genes alters in order to combat aberrant biomechanics, and that this is epigenetically regulated. However, carriage of the OA risk–conferring allele at this locus hinders this response and contributes to disease development. [ABSTRACT FROM AUTHOR]

Background: While the genetics of obesity has been well defined, the epigenetics of obesity is poorly understood. Here, we used a genome-wide approach to identify genes with differences in both DNA methylation and expression associated with a high-fat diet in mice. Results: We weaned genetically identical Small (SM/J) mice onto a high-fat or low-fat diet and measured their weights weekly, tested their glucose and insulin tolerance, assessed serum biomarkers, and weighed their organs at necropsy. We measured liver gene expression with RNA-seq (using 21 total libraries, each pooled with 2 mice of the same sex and diet) and DNA methylation with MRE-seq and MeDIP-seq (using 8 total libraries, each pooled with 4 mice of the same sex and diet). There were 4356 genes with expression differences associated with diet, with 184 genes exhibiting a sex-by-diet interaction. Dietary fat dysregulated several pathways, including those involved in cytokine-cytokine receptor interaction, chemokine signaling, and oxidative phosphorylation. Over 7000 genes had differentially methylated regions associated with diet, which occurred in regulatory regions more often than expected by chance. Only 5–10% of differentially methylated regions occurred in differentially expressed genes, however this was more often than expected by chance (p = 2.2 × 10− 8). Conclusions: Discovering the gene expression and methylation changes associated with a high-fat diet can help to identify new targets for epigenetic therapies and inform about the physiological changes in obesity. Here, we identified numerous genes with altered expression and methylation that are promising candidates for further study. [ABSTRACT FROM AUTHOR]

We investigated maternal obesity in inbred SM/J mice by assigning females to a high-fat diet or a low-fat diet at weaning, mating them to low-fat-fed males, cross-fostering the offspring to low-fat-fed SM/J nurses at birth, and weaning the offspring onto a high-fat or low-fat diet. A maternal high-fat diet exacerbated obesity in the high-fat-fed daughters, causing them to weigh more, have more fat, and have higher serum levels of leptin as adults, accompanied by dozens of gene expression changes and thousands of DNA methylation changes in their livers and hearts. Maternal diet particularly affected genes involved in RNA processing, immune response, and mitochondria. Between one-quarter and one-third of differentially expressed genes contained a differentially methylated region associated with maternal diet. An offspring high-fat diet reduced overall variation in DNA methylation, increased body weight and organ weights, increased long bone lengths and weights, decreased insulin sensitivity, and changed the expression of 3,908 genes in the liver. Although the offspring were more affected by their own diet, their maternal diet had epigenetic effects lasting through adulthood, and in the daughters these effects were accompanied by phenotypic changes relevant to obesity and diabetes. [ABSTRACT FROM AUTHOR]

Bone is a major organ in the skeletal system that supports and protects muscles and other organs, facilitates movement and hematopoiesis, and forms a reservoir of minerals including calcium. The cells in the bone, such as osteoblasts, osteoclasts, and osteocytes, orchestrate sequential and balanced regulatory mechanisms to maintain bone and are capable of differentiating in bones. Bone development and remodeling require a precise regulation of gene expressions in bone cells, a process governed by epigenetic mechanisms such as histone modification, DNA methylation, and chromatin structure. Importantly, lineage-specific transcription factors can determine the epigenetic regulation of bone cells. Emerging data suggest that perturbation of epigenetic programs can affect the function and activity of bone cells and contributes to pathogenesis of bone diseases, including osteoporosis. Thus, understanding epigenetic regulations in bone cells would be important for early diagnosis and future therapeutic approaches. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system that involves several not yet fully elucidated pathophysiologic mechanisms. There is increasing evidence that epigenetic modifications at level of DNA bases, histones, and micro-RNAs may confer risk for MS. DNA methylation seems to have a prominent role in the epigenetics of MS, as aberrant methylation in the promoter regions across genome may underlie several processes involved in the initiation and development of MS. In the present review, we discuss current understanding regarding the role of DNA methylation in MS, possible therapeutic implications and future emerging issues. [ABSTRACT FROM AUTHOR]

Background: Intersexual genomic conflict sometimes leads to unequal expression of paternal and maternal alleles in offspring, resulting in parent-of-origin effects. In honey bees reciprocal crosses can show strong parent-of-origin effects, supporting theoretical predictions that genomic imprinting occurs in this species. Mechanisms behind imprinting in honey bees are unclear but differential DNA methylation in eggs and sperm suggests that DNA methylation could be involved. Nonetheless, because DNA methylation is multifunctional, it is difficult to separate imprinting from other roles of methylation. Here we use a novel approach to investigate parent-of-origin DNA methylation in honey bees. In the subspecies Apis mellifera capensis, reproduction of females occurs either sexually by fertilization of eggs with sperm, or via thelytokous parthenogenesis, producing female embryos derived from two maternal genomes. Results: We compared genome-wide methylation patterns of sexually-produced, diploid embryos laid by a queen, with parthenogenetically-produced diploid embryos laid by her daughters. Thelytokous embryos inheriting two maternal genomes had fewer hypermethylated genes compared to fertilized embryos, supporting the prediction that fertilized embryos have increased methylation due to inheritance of a paternal genome. However, bisulfite PCR and sequencing of a differentially methylated gene, Stan (GB18207) showed strong allele-specific methylation that was maintained in both fertilized and thelytokous embryos. For this gene, methylation was associated with haplotype, not parent of origin. Conclusions: The results of our study are consistent with predictions from the kin theory of genomic imprinting. However, our demonstration of allele-specific methylation based on sequence shows that genome-wide differential methylation studies can potentially confound imprinting and allele-specific methylation. It further suggests that methylation patterns are heritable or that specific sequence motifs are targets for methylation in some genes. [ABSTRACT FROM AUTHOR]

The development of multiple sclerosis ( MS) is based on complex interactions between genetic and environmental factors. Epigenetic regulation is a biological phenomenon defined as the modification of gene expression without alteration of the DNA sequence, and is currently thought to underlie the interactions between the genetic and environmental risks of MS. The molecular mechanisms of epigenetics include DNA methylation, histone modification, and micro RNAs. Observational data obtained from epidemiological studies of MS, such as the parent-of-origin effect and the longitudinal increase in female patients, suggest that epigenetic mechanisms are involved in MS development, although the molecular basis remains unclear. Interestingly, environmental factors related to the development of MS, such as Epstein-Barr virus, smoking, and vitamin D, have been shown to regulate gene expression through epigenetic mechanisms in some experimental settings. One study showed no reproducible differences among DNA methylation profiles in peripheral blood CD4+ T cells between three monozygotic twin pairs discordant for MS. However, several studies have shown that dysregulated DNA methylation of genes is related to abnormal immune reactions and post-translational modifications of myelin proteins in MS brain samples. In addition, abnormal micro RNA profiles have been reported in brain tissues and peripheral blood immune cells obtained from MS patients. In this article, we will review the studies on the epigenetics of MS and discuss the perspectives for future research. [ABSTRACT FROM AUTHOR]

All reproductively competent adults have gone through puberty. While key genes and signaling pathways that lead to the onset of sexual maturation are known, the molecular mechanisms that determine when an individual enters puberty are only beginning to be understood. Both genetic and environmental factors determine the timing of puberty. New advances in understanding how environmentally sensitive, yet highly heritable developmental processes are regulated have come from the field of epigenetics. Of note, studies investigating the epigenetic control of the onset of puberty suggest that epigenetic repression of key inhibitory loci may play a fundamental role in the initiation of puberty. Current technologies that not only read out the DNA sequence, but also determine how the DNA is modified in response to the environment, promise new insight into how puberty is regulated, including the identification and understanding of gene regulatory networks that control the biological pathways affecting pubertal timing. Here we review the findings to date and discuss how epigenetic investigation can further our understanding of this fundamental aspect of human development. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Social environmental conditions, particularly the experience of social adversity, have long been connected with health and mortality in humans and other social mammals. Efforts to identify the physiological basis for these effects have historically focused on their neurological, endocrinological, and immunological consequences. Recently, this search has been extended to understanding the role of gene regulation in sensing, mediating, and determining susceptibility to social environmental variation. Studies in laboratory rodents, captive primates, and human populations have revealed correlations between social conditions and the regulation of a large number of genes, some of which are likely causal. Gene expression responses to the social environment are, in turn, mediated by a set of underlying regulatory mechanisms, of which epigenetic marks are the best studied to date. Importantly, a number of genes involved in the response to the social environment are also associated with susceptibility to other external stressors, as well as certain diseases. Hence, gene regulatory studies are a promising avenue for understanding, and potentially developing strategies to address, the effects of social adversity on health. [ABSTRACT FROM AUTHOR]

Background: The highly improved cognitive function is the most significant change in human evolutionary history. Recently, several large-scale studies reported the evolutionary roles of DNA methylation; however, the role of DNA methylation on brain evolution is largely unknown. Results: To test if DNA methylation has contributed to the evolution of human brain, with the use of MeDIP-Chip and SEQUENOM MassARRAY, we conducted a genome-wide analysis to identify differentially methylated regions (DMRs) in the brain between humans and rhesus macaques. We first identified a total of 150 candidate DMRs by the MeDIP-Chip method, among which 4 DMRs were confirmed by the MassARRAY analysis. All 4 DMRs are within or close to the CpG islands, and a MIR3 repeat element was identified in one DMR, but no repeat sequence was observed in the other 3 DMRs. For the 4 DMR genes, their proteins tend to be conserved and two genes have neural related functions. Bisulfite sequencing and phylogenetic comparison among human, chimpanzee, rhesus macaque and rat suggested several regions of lineage specific DNA methylation, including a human specific hypomethylated region in the promoter of K6IRS2 gene. Conclusions: Our study provides a new angle of studying human brain evolution and understanding the evolutionary role of DNA methylation in the central nervous system. The results suggest that the patterns of DNA methylation in the brain are in general similar between humans and non-human primates, and only a few DMRs were identified. [ABSTRACT FROM AUTHOR]

Background: Genomic imprinting refers to parent-of-origin dependent gene expression caused by differential DNA methylation of the paternally and maternally derived alleles. Imprinting is increasingly recognized as an important source of variation in complex traits, however, its role in explaining variation in muscle and physiological traits, especially those of commercial value, is largely unknown compared with genetic effects. Results: We investigated both genetic and genomic imprinting effects on key muscle traits in mice from the Berlin Muscle Mouse population, a key model system to study muscle traits. Using a genome scan, we first identified loci with either imprinting or genetic effects on phenotypic variation. Next, we established the proportion of phenotypic variation explained by additive, dominance and imprinted QTL and characterized the patterns of effects. In total, we identified nine QTL, two of which show large imprinting effects on glycogen content and potential, and body weight. Surprisingly, all imprinting patterns were of the bipolar type, in which the two heterozygotes are different from each other but the homozygotes are not. Most QTL had pleiotropic effects and explained up to 40% of phenotypic variance, with individual imprinted loci accounting for 4-5% of variation alone. Conclusion: Surprisingly, variation in glycogen content and potential was only modulated by imprinting effects. Further, in contrast to general assumptions, our results show that genomic imprinting can impact physiological traits measured at adult stages and that the expression does not have to follow the patterns of paternal or maternal expression commonly ascribed to imprinting effects. [ABSTRACT FROM AUTHOR]

Background/objectives: Obesity has been associated with gene methylation regulation. Recent studies have shown that epigenetic signature plays a role in metabolic homeostasis after Roux-en Y gastric bypass (RYGB). To conduct a genome-wide epigenetic analysis in peripheral blood to investigate whether epigenetic changes following RYGB stem from weight loss or the surgical procedure per se. Subjects/methods: By means of the Infinium Human Methylation 450 BeadChip array, global methylation was analyzed in blood of 24 severely obese women before and 6 months after RYGB and in 24 normal-weight women (controls). Results: In blood cells, nine DMCpG sites showed low methylation levels before surgery, methylation levels increased after RYGB and neared the levels measured in the controls. Additionally, 44 CpG sites associated with the Wnt and p53 signaling pathways were always differently methylated in the severely obese patients as compared to the controls and were not influenced by RYGB. Finally, 1638 CpG sites related to inflammation, angiogenesis, and apoptosis presented distinct methylation in the post-surgery patients as compared to the controls. Conclusion: Bariatric surgery per se acts on CpGs related to inflammation, angiogenesis, and endothelin-signaling. However, the gene cluster associated with obesity remains unchanged, suggesting that weight loss 6 months after RYGB surgery cannot promote this effect. [ABSTRACT FROM AUTHOR]

Background: DNA methylation plays a vital role in reproduction. Entire genome DNA methylation changes during the oestrous phase (ES) and dioestrous phase (DS) in the ovaries of Guanzhong dairy goats were investigated using bisulphite sequencing to understand the molecular biological mechanisms of these goats' oestrous cycle. Results: We discovered distinct genome-wide DNA methylation patterns in ES and DS ovaries. A total of 26,910 differentially methylated regions were upregulated and 21,453 differentially methylated regions were downregulated in the ES samples compared with the DS samples (P-values ≤0.05 and fold change of methylation ratios ≥2). Differentially methylated region analysis showed hypomethylation in the gene body regions and hypermethylation in the joining region between upstream regions and gene bodies. The methylation ratios of the STAR, FGF2, FGF12, BMP5 and SMAD6 genes in the ES samples were lower than those of the DS samples (P-values ≤0.05 and fold change of methylation ratios ≥2). Conversely, the methylation ratios of the EGFR, TGFBR2, IGF2BP1 and MMD2 genes increased in the ES samples compared with the DS samples. In addition, 223 differentially methylated genes were found in the GnRH signalling pathway (KO04912), ovarian steroidogenesis pathway (KO04913), oestrogen signalling pathway (KO04915), oxytocin signalling pathway (KO04921), insulin secretion pathway (KO04911) and MAPK signalling pathway (KO04010). Conclusions: This study is the first large-scale comparison of the high-resolution DNA methylation landscapes of oestrous and dioestrous ovaries from dairy goats. Previous studies and our investigations have shown that the NR5A2, STAR, FGF2 and BMP5 genes might have potential application value in regulating caprine oestrus. [ABSTRACT FROM AUTHOR]