Genome-wide DNA Methylation Levels Research Articles

Identification of Differentially Methylated Regions Associated with a Knockout of SUV39H1 in Prostate Cancer Cells

Epigenetic alterations, such as histone methylations, affect the pathogenesis of tumors including prostate cancer (PCa). Previously, we reported that metformin reduced SUV39H1, a histone methyltransferase of H3 Lys9, to inhibit the migration of PCa cells. Since histone methylation is functionally linked to DNA methylation, we speculate that the knockout of the SUV39H1 gene will affect the genomic DNA methylation profile to regulate PCa cell migration and invasion. The genome-wide DNA methylation level is lower in SUV39H1 knockout (KO) cells than wild-type (WT) ones. However, the methylation levels in functional regions of CpG Islands (CGI), 5′ untranslated region (UTR5), and exon regions are higher in KO cells than WT cells. Analysis of differentially methylated regions (DMRs) identified 1241 DMR genes that have differential methylation on CG sites when comparing the KO and WT samples. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes Pathways analysis showed that knockout of SUV39H1 affects gene sets and pathways that are heavily involved in cell shapes, cell recognition, adhesion, motility, and migration. Our study suggests that SUV39H1 plays an important role in PCa migration via the epigenetic regulation of methylation on CG sites, and is a novel and legitimate target to inhibit PCa cell migration.

Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins.

The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins Study (OATS) and explored corresponding gene expression and DNA methylation associations. 27/209 lipids (13.3%) detected by liquid chromatography-coupled mass spectrometry (LC-MS) were significantly heritable under the classical ACE twin model (h2 = 0.28-0.59), which included ceramides (Cer) and triglycerides (TG). Relative to non-significantly heritable TGs, heritable TGs had a greater number of associations with gene transcripts, not directly associated with lipid metabolism, but with immune function, signalling and transcriptional regulation. Genome-wide average DNA methylation (GWAM) levels accounted for variability in some non-heritable lipids. We reveal a complex interplay of genetic and environmental influences on the ageing plasma lipidome.

Replicated umbilical cord blood DNA methylation loci associated with gestational age at birth

ABSTRACT DNA methylation is highly sensitive to in utero perturbations and has an established role in both embryonic development and regulation of gene expression. The foetal genetic component has been previously shown to contribute significantly to the timing of birth, yet little is known about the identity and behaviour of individual genes. The aim of this study was to test the extent genome-wide DNA methylation levels in umbilical cord blood were associated with gestational age at birth (GA). Findings were validated in an independent sample and evidence for the regulation of gene expression was evaluated for cis gene relationships in specimens with multi-omic data. Genome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 450 K BeadChip, was associated with GA for 2,372 CpG probes (5% FDR) in both the Pregnancy, Race, Environment, Genes (PREG) and Newborn Epigenetic Study (NEST) cohorts. Significant probes mapped to 1,640 characterized genes and an association with nearby gene expression measures obtained by the Affymetrix HG-133A microarray was found for 11 genes. Differentially methylated positions were enriched for actively transcribed and enhancer chromatin states, were predominately located outside of CpG islands, and mapped to genes enriched for inflammation and innate immunity ontologies. In both PREG and NEST, the first principal component derived from these probes explained approximately one-half (58.1% and 47.8%, respectively) of the variation in GA. Gene pathways identified are consistent with the hypothesis of pathogen detection and response by the immune system to elicit premature labour as a consequence of unscheduled inflammation.

Genome-wide investigation of DNA methylation in congenital adrenal hyperplasia

Patients with congenital adrenal hyperplasia (CAH) are at risk of long-term cognitive and metabolic sequelae with some of the effects being attributed to the chronic glucocorticoid treatment that they receive. Our pilot study investigates genome-wide DNA methylation in patients with CAH to determine whether there is preliminary evidence for epigenomic reprogramming as well as any relationship to patient outcome. Here, we analysed CD4 + T cell DNA from 28 patients with CAH (mean age = 18.5 ± 6.5 years [y]) and 37 population controls (mean age = 17.0 ± 6.1 y) with the Infinium-HumanMethylation450 BeadChip array to measure genome-wide locus-specific DNA methylation levels. Effects of CAH, phenotype and CYP21A2 genotype on methylation were investigated as well as the association between differentially methylated CpGs and glucose homeostasis, blood lipid profile, and cognitive functions. In addition, we report data on a small cohort of 11 patients (mean age = 19.1, ±6.0 y) with CAH who were treated prenatally with dexamethasone (DEX) in addition to postnatal glucocorticoid treatment.We identified two CpGs to be associated with patient phenotype: cg18486102 (located in the FAIM2 gene; rho = 0.58, adjusted p = 0.027) and cg02404636 (located in the SFI1 gene; rho = 0.58, adjusted p = 0.038). cg02404636 was also associated with genotype (rho = 0.59, adjusted p = 0.024). Higher levels of serum C-peptide was also observed in patients with CAH (p = 0.044). Additionally, levels of C-peptide and HbA1c were positively correlated with patient phenotype (p = 0.044 and p = 0.034) and genotype (p = 0.044 and p = 0.033), respectively. No significant association was found between FAIM2 methylation and cognitive or metabolic outcome. However, SFI1 TSS methylation was associated with fasting plasma HDL cholesterol levels (p = 0.035).In conclusion, in this pilot study, higher methylation levels in CpG sites covering FAIM2 and SFI1 were associated with disease severity. Hypermethylation in these genes may have implications for long-term cognitive and metabolic outcome in patients with CAH, although the data must be interpreted with caution due to the small sample size. Additional studies in larger cohorts are therefore warranted.

Major surgery induces acute changes in measured DNA methylation associated with immune response pathways

Surgery is an invasive procedure evoking acute inflammatory and immune responses that can influence risk for postoperative complications including cognitive dysfunction and delirium. Although the specific mechanisms driving these responses have not been well-characterized, they are hypothesized to involve the epigenetic regulation of gene expression. We quantified genome-wide levels of DNA methylation in peripheral blood mononuclear cells (PBMCs) longitudinally collected from a cohort of elderly patients undergoing major surgery, comparing samples collected at baseline to those collected immediately post-operatively and at discharge from hospital. We identified acute changes in measured DNA methylation at sites annotated to immune system genes, paralleling changes in serum-levels of markers including C-reactive protein (CRP) and Interleukin 6 (IL-6) measured in the same individuals. Many of the observed changes in measured DNA methylation were consistent across different types of major surgery, although there was notable heterogeneity between surgery types at certain loci. The acute changes in measured DNA methylation induced by surgery are relatively stable in the post-operative period, generally persisting until discharge from hospital. Our results highlight the dramatic alterations in gene regulation induced by invasive surgery, primarily reflecting upregulation of the immune system in response to trauma, wound healing and anaesthesia.

Genome-wide DNA Methylation Analysis of Mantle Edge and Mantle Central from Pearl Oyster Pinctada fucata martensii.

DNA methylation is a type of epigenetic modification that alters gene expression without changing the DNA sequence and mediates some cases of phenotypic plasticity. In this study, we identified sixDNA methyltransferase (DNMT) genes and twomethyl-CpG binding domain protein2 (MBD2) gene from Pinctada fucata martensii. We also analyzed the genome-wide DNA methylation levels of mantle edge (ME) and mantle central (MC) from P. f. martensii via methylated immunoprecipitation sequencing (MeDIP-Seq). Results revealed that both ME and MC had 122 million reads, and had 58,702 and 55,721 peaks, respectively. The obtained methylation patterns of gene elements and repeats showed that the methylation of the protein-coding genes, particularly intron and coding exons (CDSs), was more frequent than that of other genomic elements in the pearl oyster genome. We combined the methylation data with the RNA-seq data of the ME and MC of P. f. martensii and found that promoter, CDS, and intron methylation levels were positively correlated with gene expression levels except the highest gene expression level. We also identified 313 differential methylation genes (DMGs) and annotated 212 of them. These DMGs were significantly enriched in 30 pathways, such as amino acid and protein metabolism, energy metabolism, terpenoid synthesis, and immune-related pathways. This study comprehensively analyzed the methylomes of biomineralization-related tissues and helped enhance our understanding of the regulatory mechanism underlying shell formation.

Integrative Network Analysis of Multi-Omics Data in the Link between Plasma Carotenoid Concentrations and Lipid Profile

Introduction: Carotenoids, which are a reliable biomarker of fruit and vegetable consumption, are positively associated with the lipid profile. Circulating carotenoid concentrations may interact with several omics profiles including genome, transcriptome, and epigenome. Few studies have used multi-omics approaches, and they rarely include environmental factors, such as diet. Objective: The objective of this observational study was to examine the potential role of multi-omics data in the interconnection between diet, represented by total carotenoids, and lipid profile using weighted gene correlation network analysis (WGCNA). Methods: Blood leukocyte DNA methylation levels of 472,245 CpG sites and whole blood gene expression levels of 18,160 transcripts were tested for associations with total carotenoid concentrations using regressions in 48 healthy subjects. WGCNA was used to identify co-omics modules and hub genes related to the lipid profile. Results: Among genes associated with total carotenoid concentrations, a total of 236 genes were identified at both DNA methylation and gene expression levels. Using WGCNA, six modules, consisting of groups of highly correlated genes represented by colors, were identified and linked to the lipid profile. Probes clustered in the turquoise and green modules correlated with plasma lipid concentrations. A total of 28 hub genes were identified. Conclusions: Genome-wide DNA methylation and gene expression levels were both associated with plasma total carotenoid concentrations. Several hub genes, mostly involved in lipid metabolism and inflammatory response with several genetic variants associated with plasma lipid concentrations, came out of the integrative analysis. This provides a comprehensive understanding of the interactive molecular system between carotenoids, omics, and plasma lipid profile.

Differences in Genome-wide DNA Methylation Profiles in Breast Milk by Race and Lactation Duration.

Black women in the United States are disproportionately affected by early-onset, triple-negative breast cancer. DNA methylation has shown differences by race in healthy and tumor breast tissues. We examined associations between genome-wide DNA methylation levels in breast milk and breast cancer risk factors, including race, to explain how this reproductive stage influences a woman's risk for, and potentially contributes to racial disparities in, breast cancer. Breast milk samples and demographic, behavioral, and reproductive data, were obtained from cancer-free, uniparous, and lactating U.S. black (n = 57) and white (n = 82) women, ages 19-44. Genome-wide DNA methylation analysis was performed on extracted breast milk DNA using the Infinium HumanMethylation450 BeadChip. Statistically significant associations between breast cancer risk factors and DNA methylation beta values, adjusting for potential confounders, were determined using linear regression followed by Bonferroni Correction (P < 1.63 × 10-7). Epigenetic analysis in breast milk revealed statistically significant associations with race and lactation duration. Of the 284 CpG sites associated with race, 242 were hypermethylated in black women. All 227 CpG sites associated with lactation duration were hypomethylated in women who lactated longer. Ingenuity Pathway Analysis of differentially methylated promoter region CpGs by race and lactation duration revealed enrichment for networks implicated in carcinogenesis. Associations between DNA methylation and lactation duration may offer insight on its role in lowering breast cancer risk. Epigenetic associations with race may mediate social, behavioral, or other factors related to breast cancer and may provide insight into potential mechanisms underlying racial disparities in breast cancer incidence.

Successful treatment of post-traumatic stress disorder reverses DNA methylation marks.

Epigenetic mechanisms play a role in the detrimental effects of traumatic stress and the development of post-traumatic stress disorder (PTSD). However, it is unknown whether successful treatment of PTSD restores these epigenetic marks. This study investigated longitudinal changes of blood-based genome-wide DNA methylation levels in relation to trauma-focused psychotherapy for PTSD in soldiers that obtained remission (N = 21), non-remitted PTSD patients (N = 23), and trauma-exposed military controls (N = 23). In an independent prospective cohort, we then examined whether these DMRs were also relevant for the development of deployment-related PTSD (N = 85). Successful treatment of PTSD was accompanied by significant changes in DNA methylation at 12 differentially methylated regions (DMRs) in the genes: APOB, MUC4, EDN2, ZFP57, GPX6, CFAP45, AFF3, TP73, UBCLP1, RPL13P, and two intergenic regions (p values < 0.0001 were confirmed using permutation and sensitivity analyses). Of the 12 DMRs related to PTSD symptom reduction, consistent prospective evidence was found for ZFP57 methylation changes related to changing PTSD symptoms (B = -0.84, t = -2.49, p = 0.014). Increasing ZFP57 methylation related to PTSD symptom reduction was present over and above the relation with symptoms, suggesting that psychological treatments exert biological effects independent of symptom reduction. Together, these data provide longitudinal evidence that ZFP57 methylation is involved in both the development and successful treatment of deployment-related PTSD. This study is a first step to disentangle the interaction between psychological and biological systems to identify genomic regions relevant for the etiology and treatment of stress-related disorders such as PTSD.

Fast Nonseparable Gaussian Stochastic Process With Application to Methylation Level Interpolation

Gaussian stochastic process (GaSP) has been widely used as a prior over functions due to its flexibility and tractability in modeling. However, the computational cost in evaluating the likelihood is , where n is the number of observed points in the process, as it requires to invert the covariance matrix. This bottleneck prevents GaSP being widely used in large-scale data. We propose a general class of nonseparable GaSP models for multiple functional observations with a fast and exact algorithm, in which the computation is linear (O(n)) and exact, requiring no approximation to compute the likelihood. We show that the commonly used linear regression and separable models are special cases of the proposed nonseparable GaSP model. Through the study of an epigenetic application, the proposed nonseparable GaSP model can accurately predict the genome-wide DNA methylation levels and compares favorably to alternative methods, such as linear regression, random forest, and localized Kriging method. The supplementary materials of this article are online and the algorithm for fast computation is implemented in the FastGaSP R package on CRAN. Supplemental materials for this article are available online.

Association of dietary folate and vitamin B-12 intake with genome-wide DNA methylation in blood: a large-scale epigenome-wide association analysis in 5841 individuals

Folate and vitamin B-12 are essential micronutrients involved in the donation of methyl groups in cellular metabolism. However, associations between intake of these nutrients and genome-wide DNA methylation levels have not been studied comprehensively in humans. The aim of this study was to assess whether folate and/or vitamin B-12 intake are asssociated with genome-wide changes in DNA methylation in leukocytes. A large-scale epigenome-wide association study of folate and vitamin B-12 intake was performed on DNA from 5841 participants from 10 cohorts using Illumina 450k arrays. Folate and vitamin B-12 intakes were calculated from food-frequency questionnaires (FFQs). Continuous and categorical (low compared with high intake) linear regression mixed models were applied per cohort, controlling for confounders. A meta-analysis was performed to identify significant differentially methylated positions (DMPs) and regions (DMRs), and a pathway analysis was performed on the DMR annotated genes. The categorical model resulted in 6 DMPs, which are all negatively associated with folate intake, annotated to FAM64A, WRAP73, FRMD8, CUX1, and LCN8 genes, which have a role in cellular processes including centrosome localization, cell proliferation, and tumorigenesis. Regional analysis showed 74 folate-associated DMRs, of which 73 were negatively associated with folate intake. The most significant folate-associated DMR was a 400-base pair (bp) spanning region annotated to the LGALS3BP gene. In the categorical model, vitamin B-12 intake was associated with 29 DMRs annotated to 48 genes, of which the most significant was a 1100-bp spanning region annotated to the calcium-binding tyrosine phosphorylation-regulated gene (CABYR). Vitamin B-12 intake was not associated with DMPs. We identified novel epigenetic loci that are associated with folate and vitamin B-12 intake. Interestingly, we found a negative association between folate and DNA methylation. Replication of these methylation loci is necessary in future studies.

DNA methylation signature of human hippocampus in Alzheimer\u2019s disease is linked to neurogenesis

BackgroundDrawing the epigenome landscape of Alzheimer’s disease (AD) still remains a challenge. To characterize the epigenetic molecular basis of the human hippocampus in AD, we profiled genome-wide DNA methylation levels in hippocampal samples from a cohort of pure AD patients and controls by using the Illumina 450K methylation arrays.ResultsUp to 118 AD-related differentially methylated positions (DMPs) were identified in the AD hippocampus, and extended mapping of specific regions was obtained by bisulfite cloning sequencing. AD-related DMPs were significantly correlated with phosphorylated tau burden. Functional analysis highlighted that AD-related DMPs were enriched in poised promoters that were not generally maintained in committed neural progenitor cells, as shown by ChiP-qPCR experiments. Interestingly, AD-related DMPs preferentially involved neurodevelopmental and neurogenesis-related genes. Finally, InterPro ontology analysis revealed enrichment in homeobox-containing transcription factors in the set of AD-related DMPs.ConclusionsThese results suggest that altered DNA methylation in the AD hippocampus occurs at specific regulatory regions crucial for neural differentiation supporting the notion that adult hippocampal neurogenesis may play a role in AD through epigenetic mechanisms.Graphical abstract

Network Analysis of the Potential Role of DNA Methylation in the Relationship between Plasma Carotenoids and Lipid Profile.

Variability in plasma carotenoids may be attributable to several factors including genetic variants and lipid profile. Until now, the impact of DNA methylation on this variability has not been widely studied. Weighted gene correlation network analysis (WGCNA) is a systems biology method used for finding gene clusters (modules) with highly correlated methylation levels and for relating them to phenotypic traits. The objective of the present study was to examine the role of DNA methylation in the relationship between plasma total carotenoid concentrations and lipid profile using WGCNA in 48 healthy subjects. Genome-wide DNA methylation levels of 20,687 out of 472,245 CpG sites in blood leukocytes were associated with total carotenoid concentrations. Using WGCNA, nine co-methylation modules were identified. A total of 2734 hub genes (17 unique top hub genes) were potentially related to lipid profile. This study provides evidence for the potential implications of gene co-methylation in the relationship between plasma carotenoids and lipid profile. Further studies and validation of the hub genes are needed.

Seasonal DNA Methylation Variation in the Flat Tree Oyster Isognomon Alatus from a Mangrove Ecosystem in North Biscayne Bay, Florida

Epigenetic analyses constitute an emerging approach for better understanding of the mechanisms underlying environmental responses and their role during acclimatization and adaptation across diverse ecosystems. The expansion of environmental epigenetic studies to a broader range of ecologically and environmentally relevant organisms will enhance the capability to forecast ecological and evolutionary processes, as well as to facilitate a retrospective assessment of stress exposures in biomonitor organisms through “epigenetic footprinting” analyses. With such purpose, the present study monitored spatial and temporal variation in abiotic parameters (temperature, salinity, pH, and horizontal visibility) over a 2-y period in a mangrove ecosystem located in North Biscayne Bay (North Miami, FL). The obtained data were subsequently compared with epigenetic modifications (global genome-wide DNA methylation levels) in the flat tree oyster Isognomon alatus, used as a sentinel model organism across experimental sites. The obtained results revealed a certain level of seasonality in temporal DNA methylation patterns, which seem to be primarily associated with changes in temperature and horizontal visibility. These results constitute the first long-term study combining spatial and temporal epigenetic analyses in a marine organism in its natural environment, laying the initial groundwork to assess the biomonitoring potential of environmental epigenetic analyses.

Childhood adversity and DNA methylation in two population-based cohorts

Childhood adversity affects later health, but the underlying molecular mechanisms are unclear. Although there is some evidence from animal models and case-control studies of a role for DNA methylation, evidence from human population-based studies is limited. In two cohorts (mothers from the Avon Longitudinal Study of Parents and Children, ALSPAC, n = 780 and women from the MRC National Survey of Health and Development, NSHD, n = 552), we assessed the association of seven adverse childhood experiences (ACEs: parental physical illness, parental mental illness, parental death, parental separation, suboptimal maternal bonding, childhood illness and child maltreatment) as well as their combination (ACE score) with genome-wide DNA methylation levels measured using the Illumina Infinium HumanMethylation450 BeadChip in peripheral blood at mean age 47 years (ALSPAC) and in buccal cells at age 53 years (NSHD). CpG sites with a genome-wide false discovery rate (FDR) below 0.05 and differentially methylated regions (DMRs) with one-step Šidák correction p-values below 0.05 in each cohort were examined in the other cohort. No individual CpG sites replicated across cohorts. However, nine DMRs replicated across cohorts respectively associated with the ACE score (one region), parental mental illness (two regions), parental physical illness (three regions) and parental death (three regions). These observations indicate that some adverse childhood experiences, notably those related to parental health, may leave imprints on peripheral DNA methylation that persist to mid-life.

Single-cell multiomics sequencing and analyses of human colorectal cancer

Although genomic instability, epigenetic abnormality, and gene expression dysregulation are hallmarks of colorectal cancer, these features have not been simultaneously analyzed at single-cell resolution. Using optimized single-cell multiomics sequencing together with multiregional sampling of the primary tumor and lymphatic and distant metastases, we developed insights beyond intratumoral heterogeneity. Genome-wide DNA methylation levels were relatively consistent within a single genetic sublineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 patients whose DNA we sequenced. The cancer cells' DNA demethylation degrees clearly correlated with the densities of the heterochromatin-associated histone modification H3K9me3 of normal tissue and those of repetitive element long interspersed nuclear element 1. Our work demonstrates the feasibility of reconstructing genetic lineages and tracing their epigenomic and transcriptomic dynamics with single-cell multiomics sequencing.

Epigenetic outlier profiles in depression: A genome-wide DNA methylation analysis of monozygotic twins.

Recent discoveries highlight the importance of stochastic epigenetic changes, as indexed by epigenetic outlier DNA methylation signatures, as a valuable tool to understand aberrant cell function and subsequent human pathology. There is evidence of such changes in different complex disorders as diverse as cancer, obesity and, to a lesser extent, depression. The current study was aimed at identifying outlying DNA methylation signatures of depressive psychopathology. Here, genome-wide DNA methylation levels were measured (by means of Illumina Infinium HumanMethylation450 Beadchip) in peripheral blood of thirty-four monozygotic twins informative for depressive psychopathology (lifetime DSM-IV diagnoses). This dataset was explored to identify outlying epigenetic signatures of depression, operationalized as extreme hyper- or hypo-methylation in affected co-twins from discordant pairs that is not observed across the rest of the study sample. After adjusting for blood cell count, there were thirteen CpG sites across which depressed co-twins from the discordant pairs exhibited outlying DNA methylation signatures. None of them exhibited a methylation outlier profile in the concordant and healthy pairs, and some of these loci spanned genes previously associated with neuropsychiatric phenotypes, such as GHSR and KCNQ1. This exploratory study provides preliminary proof-of-concept validation that epigenetic outlier profiles derived from genome-wide DNA methylation data may be related to depression risk.

Methylation Marks to Inform Association between Early-Life Air Pollution Exposures and Child Body Mass Index: An Analysis Based on A Priori Selected Pathways

Background: Early-life exposure to air pollution has been suggested to influence childhood growth and Body Mass Index (BMI). DNA methylation changes might explain part of this effect. Yet, methylome-wide studies with population sizes under 1000 generally suffer from lack of power. Using a priori information to reduce data dimension is an option to face this challenge.Aim: To identify genes whose methylation level is possibly implied in air pollution effect on child BMI, with a &amp;#8216;Meet in the middle&amp;#8217; approach, using a priori information from functional pathways.Methods: Among 1173 mother-infant pairs from Helix cohorts, exposures to 4 outdoor air pollutants were assessed during pregnancy and at age 7-9 years (total 16 exposures). Genome-wide DNA methylation levels in peripheral blood at 7&amp;#8211;9 years was measured using HumanMethylation450 BeadChip, with quality control, batch and cell types adjustments. We a priori considered only 2276 CpGs from genes belonging to 16 growth or obesity-relevant pathways according to KEGG pathway database. Stabilized Elasticnet regression (ENet) was used to independently assess associations of DNA methylation with exposures and BMI. We identified exposures sharing associated CpG sites with BMI and assessed their direct association with BMI using ENet.Results: Exposures were associated with 358 CpG loci; 12 exposures were associated with CpGs also associated with BMI (total, 22 CpGs). One of these exposures, PM10 level the day before blood collection, was associated with BMI. This exposure was associated with 62 CpGs, 2 of which being also associated with BMI, on PIK3CA (thyroid hormone signaling pathway) and ELOVL3 genes (fatty acid elongation pathway).Conclusion: Our hypothesis-generating approach identified 358 CpGs from BMI-relevant pathways associated with air pollutants, including 22 related to child BMI. These CpGs provide hints as to which genes may be implied in mechanisms underlying air pollution effects on child growth.

Genome-wide DNA methylation analysis of the regenerative and non-regenerative tissues in sika deer (Cervus nippon)

Deer antlers, the secondary organs of deer, are a unique model to study regeneration of organ/tissue in mammals. Pedicle periosteum (PP) is the key tissue type for antler regeneration. Based on our previous study, the DNA methylation was found to be the basic molecular mechanism underlying the antler regeneration. In this study, we compare the genome-wide DNA methylation level in regenerative tissues (the potentiated PP of antler, muscle, heart and liver) and non-regenerative tissue (the dormant PP) of deer by the fluorescence-labeled methylation-sensitive amplified polymorphism (F-MSAP) method. Our results showed that DNA methylation level was significantly lower in the regenerative tissues compared to the non-regenerative tissue (P < 0.05). Furthermore, 26 T-DMRs which displayed different methylated status in regenerative and non-regenerative tissues were identified by the MSAP method, and were further confirmed by Southern blot analysis. Taken together, our data suggest that DNA methylation, an important epigenetic regulation mechanism, may play an important role in the mammalian tissue/organ regeneration.

Epigenetic control of defense genes following MeJA-induced priming in rice (O. sativa)

In plant defense, priming is a physiological process by which a plant prepares to more quickly or aggressively respond to a future biotic or abiotic stress. This unique physiological state can be induced by beneficial microbes or by treatment with natural or synthetic compounds. Priming has been described copiously, mainly in dicots, but the study on the molecular mechanisms regulating the phenomenon is still at its infancy. A fascinating possibility is that epigenetic changes may be the main actors on priming establishment. A more accessible chromatin structure, due to DNA methylation and/or histone modifications, could facilitate a quicker and more potent gene response to a subsequent attack. Here, we investigated the impact of methyl jasmonate (MeJA)-induced priming on the response efficacy to mechanical wounding of a monocot (Oryza sativa). In particular, we showed that MeJA primes plants for increased expression of defense-related genes, such as OsBBPI and OsPOX, upon wounding. Finally, we provided evidence that MeJA modulates histone modifications in the promoter region of OsBBPI, as well as changes at genome-wide DNA methylation level. Together these studies corroborate the importance of priming in strengthening plant defense and support the growing evidence that epigenetic regulation plays a pivotal role in priming onset.