Refeeding with different levels of dietary carbohydrate modulates epigenetic stability through global DNA (de)methylation and histone modifications in juvenile and adult Nile tilapia (Oreochromis niloticus)

Effects of refeeding with low- or high-carbohydrate diets on intermediary carbohydrate metabolism in juvenile and adult Nile tilapia

In 2014, Facebook and Apple announced that they would pay for female employees to have their oocytes frozen to allow them to delay having children and instead focus on their careers. Whatever motivated the companies to make their offers, the fact that they did so highlights a prevalent problem faced by many young women: Their most fertile years are also a crucial period for building a career, when time off work may disadvantage them. > … cryopreservation is known to affect cell survival after thawing, which can have an impact on the subsequent clinical applications of frozen cells. To fulfill their offers, Facebook and Apple will need to offer their employees access to cryopreservation technologies that profoundly change the dynamics of family planning. Such technologies are not new, but work over the past decades has been aimed at increasing safety and efficacy and has reduced costs to the point that companies can now offer cryopreservation as a way to attract and retain female workers. Of course, the potential of cryopreservation goes far beyond freezing the eggs or sperm of ambitious young technology workers—it is a ubiquitous technology used in research and medicine for a wide variety of applications (Fig 1). For example, cryopreservation is used to store and transport biological material, including adult stem cells or stem cells from umbilical cord blood or bone marrow—both of which can later be used to treat disease or extend lifespan in the same patient—blood donations, especially of rare blood types, tissues, and organs. It is also offered as a crucial service for cancer patients to preserve their gametes before they undergo therapy that may render them infertile and, generally used in assisted reproduction to store oocytes, fertilized eggs, or embryos. Cryopreservation can contribute to environmental preservation efforts, where it is used to conserve the …

The role of global and regional DNA methylation and histone modifications in glycemic traits and type 2 diabetes: A systematic review

Chronic exposures to arsenic and estrogen are known risk factors for prostate cancer. Though the evidence suggests that exposure to arsenic or estrogens can disrupt normal DNA methylation patterns and histone modifications, the mechanisms by which these chemicals induce epigenetic changes are not fully understood. Moreover, the epigenetic effects of co-exposure to these two chemicals are not known. Therefore, the objective of this study was to evaluate the effects of chronic exposure to arsenic and estrogen, both alone and in combination, on the expression of epigenetic regulatory genes, their consequences on DNA methylation, and histone modifications. Human prostate epithelial cells, RWPE-1, chronically exposed to arsenic and estrogen alone and in combination were used for analysis of epigenetic regulatory genes expression, global DNA methylation changes, and histone modifications at protein level. The result of this study revealed that exposure to arsenic, estrogen, and their combination alters the expression of epigenetic regulatory genes and changes global DNA methylation and histone modification patterns in RWPE-1 cells. These changes were significantly greater in arsenic and estrogen combination treated group than individually treated group. The findings of this study will help explain the epigenetic mechanism of arsenic- and/or estrogen-induced prostate carcinogenesis.

Fumonisin B1 (FB1) poses a risk to animal and human health. Although the effects of FB1 on sphingolipid metabolism are well documented, there are limited studies covering the epigenetic modifications and early molecular alterations associated with carcinogenesis pathways caused by FB1 nephrotoxicity. The present study investigates the effects of FB1 on global DNA methylation, chromatin-modifying enzymes, and histone modification levels of the p16 gene in human kidney cells (HK-2) after 24 h exposure. An increase (2.23-fold) in the levels of 5-methylcytosine (5-mC) at 100 µmol/L was observed, a change independent from the decrease in gene expression levels of DNA methyltransferase 1 (DNMT1) at 50 and 100 µmol/L; however, DNMT3a and DNMT3b were significantly upregulated at 100 µmol/L of FB1. Dose-dependent downregulation of chromatin-modifying genes was observed after FB1 exposure. In addition, chromatin immunoprecipitation results showed that 10 µmol/L of FB1 induced a significant decrease in H3K9ac, H3K9me3 and H3K27me3 modifications of p16, while 100 µmol/L of FB1 caused a significant increase in H3K27me3 levels of p16. Taken together, the results suggest that epigenetic mechanisms might play a role in FB1 carcinogenesis through DNA methylation, and histone and chromatin modifications.

Background:Osteoarthritis (OA) remains one of the most common osteopathy for centuries, which can be attributed to multiple risk factors including mechanical and biochemical ones. More and more studies verified that inflammatory cytokines play important roles in the progression of OA, such as tumor necrosis factor-alpha (TNF-α). In this study, we aimed to investigate the relationship between epigenetic manifestations of TNF-? and the pathogenesis of OA.Methods:Totally, 37 OA patients’ cartilage was collected through the knee joint and 13 samples of articular cartilage as healthy control was collected through traumatic amputation. Real-time PCR, Western blot and ELISA analysis were performed to observe the expression of target genes and proteins in collected samples.Results:Compared with the healthy control group, TNF-? was over-expressing in cartilage which was collected from OA patients. DNA hypomethylation, histone hyperacetylation and histone methylation were observed in the TNF-? promoter in OA compared with normal patients, and we also studied series of enzymes associated with epigenetics. The results showed that by increasing DNA methylation and decreasing histone acetylation in the TNF-? promoter, and TNF-? over-expression in OA cartilage was suppressed, histone methylation has no significant correlation with OA.Conclusion:In conclusion, the changes of epigenetic status regulate TNF-α expression in the cells, which are pivotal to the OA disease process. These results may give us a better understanding of OA and may provide new therapeutic options.

The objective of our study was to assess the apparent digestibility of plant ingredients in diets for juvenile (50 g) and adult (220 g) Nile tilapia (Oreochromis niloticus). Dietary dry matter and protein apparent digestibility coefficients of four plant-derived feedstuffs (chickpea, maize, high-quality maize protein, and beans) were tested. The beans diet had the lowest apparent digestibility coefficient of dry matter (ADCDM) (69.41%), while no significant differences were detected in ADCDM among the other diets; ADCDM was significantly higher in adults compared with juveniles (77.02 vs. 73.76%). Apparent dry matter digestibility coefficient of ingredients (ADCI) was significantly higher in the chickpea (70.48%) and high-quality protein maize (71.09%) ingredients, and lower in the beans (52.79%) ingredient. Apparent dry matter digestibility coefficient of ingredients was significantly higher in juveniles compared with adults (72.56 vs. 56.80%). The protein digestibility of diet (ADCCP) was significantly higher in the reference diet (93.68%), while the lowest corresponded to the maize (87.86%) and beans (87.29%) diets. Significantly lower apparent digestibility coefficient of protein (ADCICP ) was obtained with the high-quality maize protein (59.11%) and maize (49.48%) ingredients, while higher ADCICP was obtained with the chickpea and beans ingredients (71.31 and 63.89%, respectively). The apparent digestibility coefficient of ingredient crude protein ADCICP was significantly higher in juveniles compared with adults (67.35 vs. 53.46). Digestibility is generally higher in juveniles, and we recommend using chickpea as an ingredient in diets for Nile tilapia.

Epigenetics in evolution and disease

Background: Periodontitis is a chronic inflammatory disease involving an interplay between bacteria, inflammation, host response genes, and environmental factors. The manifestation of epigenetic factors during periodontitis pathogenesis and periodontal inflammation is still not well understood, with limited reviews on histone modification with periodontitis management. This scoping review aims to evaluate current evidence of global and specific DNA methylation and histone modification in periodontitis and discuss the gaps and implications for future research and clinical practice. Methods: A scoping literature search of three electronic databases was performed in SCOPUS, MEDLINE (PubMed) and EMBASE. As epigenetics in periodontitis is an emerging research field, a scoping review was conducted to identify the extent of studies available and describe the overall context and applicability of these results. Results: Overall, 30 studies were evaluated, and the findings confirmed that epigenetic changes in periodontitis comprise specific modifications to DNA methylation patterns and histone proteins modification, which can either dampen or promote the inflammatory response to bacterial challenge. Conclusions: The plasticity of epigenetic modifications has implications for the future development of targeted epi-drugs and diagnostic tools in periodontitis. Such advances could be invaluable for the early detection and monitoring of susceptible individuals.

The growth and differentiation factor Myostatin (MSTN, also known as GDF8) negatively regulates skeletal muscle development and growth in vertebrates. Most fish genomes contain two or more mstn genes, which are expressed in muscle and other tissues. Yet, in the genome of Nile tilapia (Oreochromis niloticus), which is one of the world's most important aquaculture fish species, only one mstn gene has previously been identified. Here, we identify a second mstn gene in Nile tilapia. We show that it clusters phylogenetically with other piscine mstn2 genes and that it shares chromosomal synteny with the human and zebrafish orthologs. We further show that mstn2 is not expressed in red or white muscles of Nile tilapia, but rather that its main site of expression is the brain. To determine which physiological functions are correlated with mstn expression, adult Nile tilapia were exposed to various environmental conditions and their effect on mstn1 and mstn2 expression in the brain and muscles was measured using real-time PCR. We found that the centrally- and muscle-expressed mstn genes differ in their responsiveness to diverse challenges, suggesting differential gene- and tissue-specific regulation of their expression. Metabolic and stress marker analyses showed that the altered mstn expression is not regulated by classical stress response. Taken together, our findings expand the understanding of the MSTN system in Nile tilapia and provide evolutionary insight into its function.

Alzheimer's disease (AD) and bipolar disorder (BD) are progressive brain disorders. Upregulated mRNA and protein levels of neuroinflammatory and arachidonic acid (AA) markers with loss of synaptic markers (synaptophysin and drebrin) have been reported in brain tissue from AD and BD patients. We hypothesized that some of these changes are associated with epigenetic modifications of relevant genes. To test this, we measured gene-specific CpG methylation, global DNA methylation and histone modifications in postmortem frontal cortex from BD (n=10) and AD (n=10) patients and respective age-matched controls (10 per group). AD and BD brains showed several epigenetic similarities, including global DNA hypermethylation, and histone H3 phosphorylation. These changes were associated with hypo- and hypermethylation of CpG islands in cyclooxygenase-2 and brain-derived neurotrophic factor promoter regions, respectively. Only the AD brain showed hyper- and hypomethylated CpG islands in promoter regions for cAMP response element-binding protein and nuclear transcription factor kappa B genes, respectively. Only the BD brain demonstrated increased global histone H3 acetylation and hypermethylation of the promotor region for the drebrin-like protein gene. There was no significant epigenetic modification for 12-lipooxygenase or p450 epoxygenase in either illness. Many observed epigenetic changes were inversely related to respective changes in mRNA and protein levels. These epigenetic modifications involving neuroinflammatory, AA cascade and synaptic markers may contribute to progression in AD and BD and identify new targets for drug development.

Objectives: The transition from acute low back pain (aLBP) to chronic LBP (cLBP) results from a variety of factors, including epigenetic modifications of DNA. The aim of this study was to (1) compare global DNA (gDNA) methylation and histone acetylation at LBP onset between the aLBP and cLBP participants, (2) compare mRNA expression of genes with known roles in the transduction, maintenance, and/or modulation of pain between the aLBP and cLBP participants, (3) compare somatosensory function and pain ratings in our participants, and (4) determine if the aforementioned measurements were associated.Methods: A total of 220 participants were recruited for this prospective observational study following recent onset of an episode of LBP. We retained 45 individuals whose gDNA was of sufficient quality for analysis. The final sample included 14 participants whose pain resolved within 6 weeks of onset (aLBP),15 participants that reported pain for 6 months (cLBP), and 16 healthy controls. Participants were subjected to quantitative sensory testing (QST), blood was drawn via venipuncture, gDNA isolated, and global DNA methylation and histone acetylation, as well as mRNA expression of 84 candidate genes, were measured.Results: Individuals that develop cLBP display multimodal somatosensory hypersensitivity relative to aLBP participants. cLBP participants also had significantly lower global DNA methylation, which was negatively correlated with interleukin-2 (IL2) mRNA expression.Discussion: cLBP is characterized by somatosensory hypersensitivity, lower global DNA methylation, and higher IL2 expression level compared to those whose pain will resolve quickly (aLBP). These results suggest potential diagnostic and therapeutic relevance for global DNA methylation and IL2 expression in the pathology underlying the transition from acute to chronic LBP.

Nuclear events such as chromatin condensation, DNA cleavage at internucleosomal sites, and histone release from chromatin are recognized as hallmarks of apoptosis. However, there is no complete understanding of the molecular events underlying these changes. It is likely that epigenetic changes such as DNA methylation and histone modifications that are involved in chromatin dynamics and structure are also involved in the nuclear events described. In this report we have shown that apoptosis is associated with global DNA hypomethylation and histone deacetylation events in leukemia cells. Most importantly, we have observed a particular epigenetic signature for early apoptosis defined by a release of hypoacetylated and trimethylated histone H4 and internucleosomal fragmented DNA that is hypermethylated and originates from perinuclear heterochromatin. These findings provide one of the first links between apoptotic nuclear events and epigenetic markers.

An elevated level of homocysteine (Hyperhomocysteinemia) is associated with increased risk factor of neurological disorder. Homocysteine (Hcy) modulates cellular methylation reactions. Previously we have demonstrated that HHcy caused significant metabolic changes and altered mitochondrial function in mouse brain endothelial cells (bEND3). However, the mechanisms behind such alterations remain unclear. The present study examined if the effects of Hcy on mitochondria dysfunction are mediated through an epigenetic mechanism. Following exposure to Hcy for 72 h, global DNA methylation and histone H3 lysine 9 (H3K9) acetylation were examined using flow cytometric analysis. Total DNA methyltransferase activity (DNMT) and protein levels of DNMT 3 were measured. Mitochondrial respiratory capacity and mitochondrial permeability transition (MPT) were measured by fluorescence dye. The result suggested that HHcy caused global DNA hypomethylation and histone hyperacetylation. Total DNMT activity significantly decreased which was accompanied by a significant reduction in protein levels of DNMT 3 and loss of MPT. Treatment of bEND3 with the DNMT inhibitor, 5‐aza‐2′‐deoxycytidine, mimicked the functional changes induced by Hcy. This study suggests that the Hcy related metabolic changes including altered mitochondrial function may be mediated through an epigenetic mechanism.

DNA methylation and histone acetylation can be modified by various pathological or physiological factors such as hypoxia, thus influencing gene expression. In this study, we investigated the changes of global DNA methylation and histone acetylation and the related enzymes in rat brain after chronic cerebrovascular hypoperfusion by bilateral common carotid occlusion (2-VO) surgery. Colorimetric and immunohistochemistry staining were used to evaluate the global DNA methylation and histone acetylation levels, respectively. The expressions of DNA methyltransferase 1/3a (DNMT1/3a), methyl-CpG binding domain protein 2 (MBD2), histone deacetylase 3 (HDAC3) and acetyltransferase (HAT) were assessed by Western blot. We found that the level of global DNA methylation was decreased to 31.7% (P <0.01) of the sham-operated group at 10 days and increased by 30% (P <0.01) compared with the sham group at 90 days after 2-VO surgery. DNMT3a expression was down-regulated to 75.7% of the sham group, while MBD2 expression was up-regulated by 95% compared with sham group at 90 days after 2-VO. The histone H3 acetylation level was markedly decreased to 75.3% of the sham group at 10 days and 73.5% at 90 days after 2-VO, while no significant change was found for histone H4 acetylation. HDAC3 expression was markedly down-regulated to 36% of the sham group, whereas cAMP-response element binding protein expression was up-regulated by 33.6% compared with the sham group at 90 days after 2-VO. These results suggest that chronic cerebrovascular hypoperfusion influences global DNA methylation and histone acetylation levels through the related enzymes, and therefore might contribute to several neurodegenerative diseases.