scholarly journals Methylomes in Vegans versus Pescatarians and Nonvegetarians

Epigenomes ◽  
2020 ◽  
Vol 4 (4) ◽  
pp. 28
Author(s):  
Valery Filippov ◽  
Karen Jaceldo-Siegl ◽  
Alexey Eroshkin ◽  
Vasiliy Loskutov ◽  
Xin Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Regulation ◽  
Animal Models ◽  
Statistical Tests ◽  
Buffy Coat ◽  
Methylation Data ◽  
Cpg Sites ◽  
Methylation Of Dna ◽  
Methylation Patterns ◽  
Different Sources

Epigenetic studies in animal models have demonstrated that diet affects gene regulation by altering methylation patterns. We interrogated methylomes in humans who have different sources of protein in their diet. We compared methylation of DNA isolated from buffy coat in 38 vegans, 41 pescatarians and 68 nonvegetarians. Methylation data were obtained using Infinium HumanMethylation450 arrays and analyzed using the Partek Genomic software. Differences in differentially methylated sites were small, though with the use of relaxed statistical tests we did identify diet-associated differences. To further test the validity of these observations, we performed separate and independent comparisons of the methylation differences between vegans and nonvegetarians, and between vegans and pescatarians. The detected differences were then examined to determine if they were enriched in specific pathways. Pathway analysis revealed enrichment of several specific processes, including homeobox transcription and glutamate transport. The detected differences in DNA methylation patterns between vegans, pescatarians, and nonvegetarians enabled us to identify 77 CpG sites that may be sensitive to diet and/or lifestyle, though high levels of individual-specific differences were also noted.

scholarly journals Structural insights into CpG-specific DNA methylation by human DNA methyltransferase 3B

2020 ◽  
Vol 48 (7) ◽  
pp. 3949-3961 ◽  
Author(s):  
Chien-Chu Lin ◽  
Yi-Ping Chen ◽  
Wei-Zen Yang ◽  
James C K Shen ◽  
Hanna S Yuan
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Cytosine Methylation ◽  
Catalytic Domain ◽  
De Novo ◽  
Water Channel ◽  
Dna Methyltransferases ◽  
Structural Basis ◽  
Cpg Sites ◽  
Methylation Patterns

Abstract DNA methyltransferases are primary enzymes for cytosine methylation at CpG sites of epigenetic gene regulation in mammals. De novo methyltransferases DNMT3A and DNMT3B create DNA methylation patterns during development, but how they differentially implement genomic DNA methylation patterns is poorly understood. Here, we report crystal structures of the catalytic domain of human DNMT3B–3L complex, noncovalently bound with and without DNA of different sequences. Human DNMT3B uses two flexible loops to enclose DNA and employs its catalytic loop to flip out the cytosine base. As opposed to DNMT3A, DNMT3B specifically recognizes DNA with CpGpG sites via residues Asn779 and Lys777 in its more stable and well-ordered target recognition domain loop to facilitate processive methylation of tandemly repeated CpG sites. We also identify a proton wire water channel for the final deprotonation step, revealing the complete working mechanism for cytosine methylation by DNMT3B and providing the structural basis for DNMT3B mutation-induced hypomethylation in immunodeficiency, centromere instability and facial anomalies syndrome.

scholarly journals Importance of Genetic Factors in Male Fertility Disorders, Clinical Relevance of Epigenetic Markers in Male Infertility

2019 ◽  
Vol 70 (7) ◽  
pp. 2566-2570
Author(s):  
Dragos Botezatu ◽  
Cristina Popescu ◽  
Andrei-Dan Korodi ◽  
Cristian Furau ◽  
Gheorghe Furau ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Male Infertility ◽  
Male Fertility ◽  
Complex Problem ◽  
The Body ◽  
Control Group ◽  
Global Methylation ◽  
Methylation Of Dna ◽  
Genome Methylation ◽  
Methylation Patterns

Male infertility is a common and complex problem affecting 1 out of 20 men. Despite extensive research in this area, in many cases, the underlying causes are unknown. Epigenetic changes control a series of processes within the body, including male fertility. Classification of infertile men using a more detailed analysis of DNA methylation patterns could reveal a new level of low rates of fertilization, implantation, or pregnancy. In this context, it seemed to us to use the techniques available to evaluate the degree of global methylation of DNA in infertile patients who have modified sperm counts, but also those who apparently do not have a clear cause of infertility. For this we used the Quest 5mC-Zymoresaerch-ELISA kit that can detect within about 5 hours the global level of genome methylation. Claims on which common illnesses have an epigenetic base are still open to speculation, but if true, it can imprint a new direction in medicine. Our data, although from a pilot study, are consistent with those in the literature. A recent study has shown that DNA methylation levels were significantly higher in oligoasthenoteratozoospermia patients than in the control group and the increase in global DNA methylation and histone retention in men with oligoasthenoteratozoospermia.

Abstract P098: An Epigenome-wide Study of Obesity in African American Youth and Young Adults: Novel Findings, Replication in Neutrophils and Relationship With Gene Expression

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Xiaoling Wang ◽  
Yue Pan ◽  
Haidong Zhu ◽  
Guang Hao ◽  
Xin Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Older Adults ◽  
Dna Methylation ◽  
Young Adults ◽  
Methylation Data ◽  
Middle Aged ◽  
Cpg Sites ◽  
Genome Wide ◽  
Obesity Status ◽  
Youth And Young Adults

Background: Several large-scale epigenome wide association studies on obesity-related DNA methylation changes have been published and in total identified 46 CpG sites. These studies were conducted in middle-aged and older adults of Caucasians and African Americans (AAs) using leukocytes. To what extend these signals are independent of cell compositions as well as to what extend they may influence gene expression have not been systematically investigated. Furthermore, the high prevalence of obesity comorbidities in middle-aged or older population may hide or bias obesity itself related DNA methylation changes. Methods: In this study of healthy AA youth and young adults, genome wide DNA methylation data from leukocytes were obtained from three independent studies: EpiGO study (96 obese cases vs. 92 lean controls, aged 14-21, 50% females, test of interest is obesity status), LACHY study (284 participants from general population, aged 14-18, 50% females, test of interest is BMI), and Georgia Stress and Heart study (298 participants from general population, aged 18-38, 52% females, test of interest is BMI) using the Infinium HumanMethylation450 BeadChip. Genome wide DNA methylation data from purified neutrophils as well as genome wide gene expression data from leukocytes using Illumina HT12 V4 array were also obtained for the EpiGO samples. Results: The meta-analysis on the 3 cohorts identified 76 obesity related CpG sites in leukocytes with p<1х10 -7 . Out of the 46 previously identified CpG sites, 36 can be replicated in this AA youth and young adult sample with same direction and p<0.05. Out of the 107 CpG sites including the 36 replicated ones and the 71 newly identified ones, 71 CpG sites (66%) had their relationship with obesity replicated in purified neutrophils (p<0.05). The analysis on the cis regulation of the 107 CpG sites on gene expression showed that 59 CpG sites had at least one gene within 250kb having expression difference between obese cases and lean controls. Furthermore, out of the 59 CpG sites, 6 showed significantly negative correlations and 1 showed significantly positive correlation with the differentially expressed genes. These CpG sites located in SOCS3, CISH, ABCG1, PIM3 and PTGDS genes. Conclusion: In this study of AA youth and young adults, we identified novel CpG sites associated with obesity and replicated majority of the CpG sites previously identified in middle-aged and older adults. For the first time, we showed that majority of the obesity related CpG sites identified from leukocytes are not driven by cell compositions and provided the direct link between DNA methylation-gene expression-obesity status for 7 CpG sites in 5 genes.

scholarly journals Changes in DNA Methylation and Gene Expression of Insulin and Obesity-Related Gene PIK3R1 after Roux-en-Y Gastric Bypass

2020 ◽  
Vol 21 (12) ◽  
pp. 4476
Author(s):  
Marcela A S Pinhel ◽  
Natália Y Noronha ◽  
Carolina F Nicoletti ◽  
Vanessa AB Pereira ◽  
Bruno AP de Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Weight Loss ◽  
Gastric Bypass ◽  
Related Gene ◽  
Cpg Sites ◽  
Genome Wide ◽  
Genetically Determined ◽  
Methylation Patterns ◽  
Weight Loss Interventions

Weight regulation and the magnitude of weight loss after a Roux-en-Y gastric bypass (RYGB) can be genetically determined. DNA methylation patterns and the expression of some genes can be altered after weight loss interventions, including RYGB. The present study aimed to evaluate how the gene expression and DNA methylation of PIK3R1, an obesity and insulin-related gene, change after RYGB. Blood samples were obtained from 13 women (35.9 ± 9.2 years) with severe obesity before and six months after surgical procedure. Whole blood transcriptome and epigenomic patterns were assessed by microarray-based, genome-wide technologies. A total of 1966 differentially expressed genes were identified in the pre- and postoperative periods of RYGB. From these, we observed that genes involved in obesity and insulin pathways were upregulated after surgery. Then, the PIK3R1 gene was selected for further RT-qPCR analysis and cytosine-guanine nucleotide (CpG) sites methylation evaluation. We observed that the PI3KR1 gene was upregulated, and six DNA methylation CpG sites were differently methylated after bariatric surgery. In conclusion, we found that RYGB upregulates genes involved in obesity and insulin pathways.

scholarly journals Testing cell-type-specific mediation effects in genome-wide epigenetic studies

2020 ◽  
Author(s):  
Xiangyu Luo ◽  
Joel Schwartz ◽  
Andrea Baccarelli ◽  
Zhonghua Liu
Keyword(s):  
Dna Methylation ◽  
Mediation Analysis ◽  
Methylation Data ◽  
Cell Type ◽  
Multiple Testing Procedure ◽  
Mediation Effects ◽  
Cpg Sites ◽  
Genome Wide ◽  
A Cell ◽  
Cell Type Specific

Abstract Epigenome-wide mediation analysis aims to identify DNA methylation CpG sites that mediate the causal effects of genetic/environmental exposures on health outcomes. However, DNA methylations in the peripheral blood tissues are usually measured at the bulk level based on a heterogeneous population of white blood cells. Using the bulk level DNA methylation data in mediation analysis might cause confounding bias and reduce study power. Therefore, it is crucial to get fine-grained results by detecting mediation CpG sites in a cell-type-specific way. However, there is a lack of methods and software to achieve this goal. We propose a novel method (Mediation In a Cell-type-Specific fashion, MICS) to identify cell-type-specific mediation effects in genome-wide epigenetic studies using only the bulk-level DNA methylation data. MICS follows the standard mediation analysis paradigm and consists of three key steps. In step1, we assess the exposure-mediator association for each cell type; in step 2, we assess the mediator-outcome association for each cell type; in step 3, we combine the cell-type-specific exposure-mediator and mediator-outcome associations using a multiple testing procedure named MultiMed [Sampson JN, Boca SM, Moore SC, et al. FWER and FDR control when testing multiple mediators. Bioinformatics 2018;34:2418–24] to identify significant CpGs with cell-type-specific mediation effects. We conduct simulation studies to demonstrate that our method has correct FDR control. We also apply the MICS procedure to the Normative Aging Study and identify nine DNA methylation CpG sites in the lymphocytes that might mediate the effect of cigarette smoking on the lung function.

scholarly journals The Expression Level of mRNA, Protein, and DNA Methylation Status of FOSL2 of Uyghur in XinJiang in Type 2 Diabetes

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jun Li ◽  
Siyuan Li ◽  
Ying Hu ◽  
Guolei Cao ◽  
Siyao Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Methylation Status ◽  
Methylation Data ◽  
Biochemical Indicators ◽  
Expression Levels ◽  
Protein Levels ◽  
Cpg Sites

Objective. We investigated the expression levels of both FOSL2 mRNA and protein as well as evaluating DNA methylation in the blood of type 2 diabetes mellitus (T2DM) Uyghur patients from Xinjiang. This study also evaluated whether FOSL2 gene expression had demonstrated any associations with clinical and biochemical indicators of T2DM. Methods. One hundred Uyghur subjects where divided into two groups, T2DM and nonimpaired glucose tolerance (NGT) groups. DNA methylation of FOSL2 was also analyzed by MassARRAY Spectrometry and methylation data of individual units were generated by the EpiTyper v1.0.5 software. The expression levels of FOS-like antigen 2 (FOSL2) and the protein expression levels were analyzed. Results. Significant differences were observed in mRNA and protein levels when compared with the NGT group, while methylation rates of eight CpG units within the FOSL2 gene were higher in the T2DM group. Methylation of CpG sites was found to inversely correlate with expression of other markers. Conclusions. Results show that a correlation between mRNA, protein, and DNA methylation of FOSL2 gene exists among T2DM patients from Uyghur. FOSL2 protein and mRNA were downregulated and the DNA became hypermethylated, all of which may be involved in T2DM pathogenesis in this population.

Genome-Wide DNA Methylation Analysis Shows Enrichment of Differential Methylation in “Open Seas” and Enhancers and Reveals Hypomethylation in DNMT3A Mutated Cytogenetically Normal AML (CN-AML)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 653-653 ◽  
Author(s):  
Ying Qu ◽  
Andreas Lennartsson ◽  
Verena I. Gaidzik ◽  
Stefan Deneberg ◽  
Sofia Bengtzén ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cpg Island ◽  
Cpg Islands ◽  
Differential Methylation ◽  
Methylation Analysis ◽  
Cpg Sites ◽  
Genome Wide ◽  
Genomic Regions ◽  
Methylation Patterns

Abstract Abstract 653 DNA methylation is involved in multiple biologic processes including normal cell differentiation and tumorigenesis. In AML, methylation patterns have been shown to differ significantly from normal hematopoietic cells. Most studies of DNA methylation in AML have previously focused on CpG islands within the promoter of genes, representing only a very small proportion of the DNA methylome. In this study, we performed genome-wide methylation analysis of 62 AML patients with CN-AML and CD34 positive cells from healthy controls by Illumina HumanMethylation450K Array covering 450.000 CpG sites in CpG islands as well as genomic regions far from CpG islands. Differentially methylated CpG sites (DMS) between CN-AML and normal hematopoietic cells were calculated and the most significant enrichment of DMS was found in regions more than 4kb from CpG Islands, in the so called open sea where hypomethylation was the dominant form of aberrant methylation. In contrast, CpG islands were not enriched for DMS and DMS in CpG islands were dominated by hypermethylation. DMS successively further away from CpG islands in CpG island shores (up to 2kb from CpG Island) and shelves (from 2kb to 4kb from Island) showed increasing degree of hypomethylation in AML cells. Among regions defined by their relation to gene structures, CpG dinucleotide located in theoretic enhancers were found to be the most enriched for DMS (Chi χ2<0.0001) with the majority of DMS showing decreased methylation compared to CD34 normal controls. To address the relation to gene expression, GEP (gene expression profiling) by microarray was carried out on 32 of the CN-AML patients. Totally, 339723 CpG sites covering 18879 genes were addressed on both platforms. CpG methylation in CpG islands showed the most pronounced anti-correlation (spearman ρ =-0.4145) with gene expression level, followed by CpG island shores (mean spearman rho for both sides' shore ρ=-0.2350). As transcription factors (TFs) have shown to be crucial for AML development, we especially studied differential methylation of an unbiased selection of 1638 TFs. The most enriched differential methylation between CN-AML and normal CD34 positive cells were found in TFs known to be involved in hematopoiesis and with Wilms tumor protein-1 (WT1), activator protein 1 (AP-1) and runt-related transcription factor 1 (RUNX1) being the most differentially methylated TFs. The differential methylation in WT 1 and RUNX1 was located in intragenic regions which were confirmed by pyro-sequencing. AML cases were characterized with respect to mutations in FLT3, NPM1, IDH1, IDH2 and DNMT3A. Correlation analysis between genome wide methylation patterns and mutational status showed statistically significant hypomethylation of CpG Island (p<0.0001) and to a lesser extent CpG island shores (p<0.001) and the presence of DNMT3A mutations. This links DNMT3A mutations for the first time to a hypomethylated phenotype. Further analyses correlating methylation patterns to other clinical data such as clinical outcome are ongoing. In conclusion, our study revealed that non-CpG island regions and in particular enhancers are the most aberrantly methylated genomic regions in AML and that WT 1 and RUNX1 are the most differentially methylated TFs. Furthermore, our data suggests a hypomethylated phenotype in DNMT3A mutated AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Methylome-wide association study of early life stressors and adult mental health reveals a relationship between birth date and cell type composition in blood

2021 ◽  
Author(s):  
David M. Howard ◽  
Oliver Pain ◽  
Ryan Arathimos ◽  
Miruna C. Barbu ◽  
Carmen Amador ◽  
...  
Keyword(s):  
Mental Health ◽  
Dna Methylation ◽  
Early Life ◽  
Birth Date ◽  
Testing Time ◽  
Methylation Data ◽  
Adult Mental Health ◽  
Cpg Sites ◽  
Early Life Environment ◽  
Significant Difference

AbstractThe environment and events that we are exposed to in utero, during birth and in early childhood influence our future physical and mental health. The underlying mechanisms that lead to these outcomes in adulthood are unclear, but long-term changes in epigenetic marks, such as DNA methylation, could act as a mediating factor or biomarker. DNA methylation data was assayed at 713,522 CpG sites from 9,537 participants of the Generation Scotland: Scottish Family Health Study, a family-based cohort with extensive data on genetic, medical, family history and lifestyle information. Methylome-wide association studies of eight early life environment phenotypes and two adult mental health phenotypes were conducted using DNA methylation data collected from adult whole blood samples. Two genes involved with different developmental pathways (PRICKLE2 and ABI1) were annotated to CpG sites associated with preterm birth (P < 1.27 × 10 −9). A further two genes important to the development of sensory pathways (SOBP and RPGRIP1) were annotated to sites associated with low birth weight (P < 4.35 × 10−8). Genes and gene-sets annotated from associated CpGs sites and methylation profile scores were then used to quantify any overlap between the early life environment and mental health traits. However, there was no evidence of any overlap after applying a correction for multiple testing. Time of year of birth was found to be associated with a significant difference in estimated lymphocyte and neutrophil counts. Early life environments influence the risk of developing mental health disorders later in life; however, this study provides no evidence that this is mediated by stable changes to the methylome detectable in peripheral blood.

scholarly journals DNA methylation patterns of β-globin cluster in β-thalassemia patients

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiuqin Bao ◽  
Yangjin Zuo ◽  
Diyu Chen ◽  
Cunyou Zhao
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Methylation Level ◽  
Epigenetic Modification ◽  
Fetal Hemoglobin ◽  
Cpg Sites ◽  
Hbf Level ◽  
Globin Promoter ◽  
Methylation Patterns ◽  
Normal Controls

Abstract Background Reactivation of fetal hemoglobin (HbF, α2γ2) holds a therapeutic target for β-thalassemia and sickle cell disease. Although many HbF regulators have been identified, the methylation patterns in β-globin cluster driving the fetal-to-adult hemoglobin switch remains to be determined. Results Here, we evaluated DNA methylation patterns of the β-globin cluster from peripheral bloods of 105 β0/β0 thalassemia patients and 44 normal controls. We also recruited 15 bone marrows and 4 cord blood samples for further evaluation. We identified that the CpG sites in the locus control region (LCR) DNase I hypersensitive site 4 and 3 (HS4-3) regions, and γ- and β-globin promoters displayed hypomethylation in β0/β0-thalassemia patients, especially for the patients with high HbF level, as compared with normal controls. Furthermore, hypomethylations in most of CpG sites of the HS4-3 core regions were also observed in bone marrows (BM) of β0/β0-patients compared with normal controls; and methylation level of γ-globin promoter -50 and + 17 CpG sites showed lower methylation level in patients with high HbF level compared with those with low HbF level and a negative correlation with HbF level among β0-thalassemia patients. Finally, γ-globin promoter + 17 and + 50 CpG sites also displayed significant hypomethylation in cord blood (CB) tissues compared with BM tissues from normal controls. Conclusions Our findings revealed methylation patterns in β-globin cluster associated with β0 thalassemia disease and γ-globin expression, contributed to understand the epigenetic modification in β0 thalassemia patients and provided candidate targets for the therapies of β-hemoglobinopathies.

DNA methylation profiling identifies epigenetic differences between early versus late stages of diabetic chronic kidney disease

2020 ◽  
Author(s):  
Ashani Lecamwasam ◽  
Boris Novakovic ◽  
Braydon Meyer ◽  
Elif I Ekinci ◽  
Karen M Dwyer ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Dna Methylation ◽  
Kidney Disease ◽  
Secretory Protein ◽  
Differentially Methylated Region ◽  
P Value ◽  
Operating Characteristics ◽  
Cross Sectional ◽  
Cpg Sites ◽  
Methylation Patterns

Abstract Background We investigated a cross-sectional epigenome-wide association study of patients with early and late diabetes-associated chronic kidney disease (CKD) to identify possible epigenetic differences between the two groups as well as changes in methylation across all stages of diabetic CKD. We also evaluated the potential of using a panel of identified 5′-C-phosphate-G-3′ (CpG) sites from this cohort to predict the progression of diabetic CKD. Methods This cross-sectional study recruited 119 adults. DNA was extracted from blood using the Qiagen QIAampDNA Mini Spin Kit. Genome-wide methylation analysis was performed using Illumina Infinium MethylationEPIC BeadChips (HM850K). Intensity data files were processed and analysed using the minfi and MissMethyl packages for R. We examined the degree of methylation of CpG sites in early versus late diabetic CKD patients for CpG sites with an unadjusted P-value &lt;0.01 and an absolute change in methylation of 5% (n = 239 CpG sites). Results Hierarchical clustering of the 239 CpG sites largely separated the two groups. A heat map for all 239 CpG sites demonstrated distinct methylation patterns in the early versus late groups, with CpG sites showing evidence of progressive change. Based on our differentially methylated region (DMR) analysis of the 239 CpG sites, we highlighted two DMRs, namely the cysteine-rich secretory protein 2 (CRISP2) and piwi-like RNA-mediated gene silencing 1 (PIWIL1) genes. The best predictability for the two groups involved a receiver operating characteristics curve of eight CpG sites alone and achieved an area under the curve of 0.976. Conclusions We have identified distinct DNA methylation patterns between early and late diabetic CKD patients as well as demonstrated novel findings of potential progressive methylation changes across all stages (1–5) of diabetic CKD at specific CpG sites. We have also identified associated genes CRISP2 and PIWIL1, which may have the potential to act as stage-specific diabetes-associated CKD markers, and showed that the use of a panel of eight identified CpG sites alone helps to increase the predictability for the two groups.

Sign in / Sign up

Export Citation Format

Share Document