Early life lead exposure causes gender-specific changes in the DNA methylation profile of DNA extracted from dried blood spots

AbstractStudies in rodents, nonhuman primates, and humans suggest that epigenetic processes mediate between early life experiences and adult phenotype. However, the normal evolution of epigenetic programs during child development, the effect of sex, and the impact of early life adversity on these trajectories are not well understood. This study mapped the genome-wide DNA methylation changes in CD3+ T lymphocytes from rhesus monkeys from postnatal day 14 through 2 years of age in both males and females and determined the impact of maternal deprivation on the DNA methylation profile. We show here that DNA methylation profiles evolve from birth to adolescence and are sex dependent. DNA methylation changes accompany imposed weaning, attenuating the difference between males and females. Maternal separation at birth alters the normal evolution of DNA methylation profiles and targets genes that are also affected by a later stage maternal separation, that is, weaning. Our results suggest that early life events dynamically interfere with the normal developmental evolution of the DNA methylation profile and that these changes are highly effected by sex.

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Integrated analysis of DNA methylation profile in HLA-G gene and imaging in coronary heart disease

European Heart Journal ◽

10.1093/ehjci/ehaa946.1255 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

G Benincasa ◽

C Schiano ◽

T Infante ◽

M Franzese ◽

R Casale ◽

...

Keyword(s):

Dna Methylation ◽

Coronary Heart Disease ◽

Heart Disease ◽

Cpg Island ◽

Methylation Profile ◽

Integrated Analysis ◽

Funding Source ◽

Relevant Parameter ◽

Cardiac Computed Tomography Angiography ◽

Dna Methylation Profile

Abstract Aims Immune endothelial inflammation, underlie coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features. Methods Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study. Obstructive CHD group included fourteen patients, in which there was a stenosis greater than or equal to 50% in one or more of the major coronary arteries detected; whereas subjects with Calcium (Ca) Score=0, uninjured coronaries and with no obstructive CHD were considered as control subjects (Ctrls) (n=18). For both groups, DNA methylation profile of the whole 5'UTR-CpG island of HLA-G was measured. The plasma soluble HLA-G (sHLA-G) levels were detected in all subjects by specific ELISA assay. Statistical analysis was performed using R software. Results For the first time, our study reported that 1) a significant hypomethylation characterized three specific fragments (B, C and F) of the 5'UTR-CpG island (p=0.05) of HLA-G gene in CHD patients compared to Ctrl group; 2) hypomethylation level of one specific fragment positively correlated with coronary Ca score, a relevant parameter of CCTA (p<0.05) between two groups. Conclusions Our results showed that reduced levels of circulating HLA-G molecules could derive from epigenetic marks inducing hypomethylation of specific regions into 5'UTR-CpG island of HLA-G gene in CHD patients with obstructive coronary stenosis vs non critical stenosis group. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Minister of Health

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DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Communications Biology ◽

10.1038/s42003-020-01469-0 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Vanessa Lakis ◽

◽

Rita T. Lawlor ◽

Felicity Newell ◽

Ann-Marie Patch ◽

...

Keyword(s):

Dna Methylation ◽

Neuroendocrine Tumors ◽

Methylation Profile ◽

Pancreatic Neuroendocrine Tumors ◽

Wild Type ◽

Genomic Information ◽

Chromosome 11 ◽

Dna Methylation Profile ◽

Methylation Patterns ◽

Recurrent Patterns

AbstractHere we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs.

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DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults

Epigenetics ◽

10.1080/15592294.2021.1876285 ◽

2021 ◽

pp. 1-17

Author(s):

Mohamed M. Ali ◽

Dina Naquiallah ◽

Maryam Qureshi ◽

Mohammed Imaduddin Mirza ◽

Chandra Hassan ◽

...

Keyword(s):

Dna Methylation ◽

Vascular Function ◽

Methylation Profile ◽

Morbidly Obese ◽

Obese Adults ◽

Dna Methylation Profile

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Overlapping DNA methylation profile between placentas with trisomy 16 and early-onset preeclampsia

Placenta ◽

10.1016/j.placenta.2014.01.001 ◽

2014 ◽

Vol 35 (3) ◽

pp. 216-222 ◽

Cited By ~ 16

Author(s):

J.D. Blair ◽

S. Langlois ◽

D.E. McFadden ◽

W.P. Robinson

Keyword(s):

Dna Methylation ◽

Early Onset ◽

Methylation Profile ◽

Trisomy 16 ◽

Dna Methylation Profile ◽

Early Onset Preeclampsia

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Genome-wide DNA methylation profiling with MeDIP-seq using archived dried blood spots

Clinical Epigenetics ◽

10.1186/s13148-016-0242-1 ◽

2016 ◽

Vol 8 (1) ◽

Cited By ~ 22

Author(s):

Nicklas H. Staunstrup ◽

Anna Starnawska ◽

Mette Nyegaard ◽

Lene Christiansen ◽

Anders L. Nielsen ◽

...

Keyword(s):

Dna Methylation ◽

Dried Blood Spots ◽

Blood Spots ◽

Genome Wide ◽

Dna Methylation Profiling ◽

Methylation Profiling

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Perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) and DNA methylation in newborn dried blood spots in the Upstate KIDS cohort

Environmental Research ◽

10.1016/j.envres.2020.110668 ◽

2021 ◽

Vol 194 ◽

pp. 110668

Author(s):

Sonia L. Robinson ◽

Xuehuo Zeng ◽

Weihua Guan ◽

Rajeshwari Sundaram ◽

Pauline Mendola ◽

...

Keyword(s):

Dna Methylation ◽

Perfluorooctane Sulfonate ◽

Perfluorooctanoic Acid ◽

Dried Blood Spots ◽

Blood Spots

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Low-pass whole genome bisulfite sequencing of neonatal dried blood spots identifies a role for RUNX1 in Down syndrome DNA methylation profiles

Human Molecular Genetics ◽

10.1093/hmg/ddaa218 ◽

2020 ◽

Author(s):

Benjamin I Laufer ◽

Hyeyeon Hwang ◽

Julia M Jianu ◽

Charles E Mordaunt ◽

Ian F Korf ◽

...

Keyword(s):

Dna Methylation ◽

Down Syndrome ◽

Early Life ◽

Trisomy 21 ◽

Bisulfite Sequencing ◽

Dried Blood Spots ◽

Whole Genome ◽

Genome Wide ◽

Low Pass ◽

Genome Bisulfite Sequencing

Abstract Neonatal dried blood spots (NDBS) are a widely banked sample source that enables retrospective investigation into early life molecular events. Here, we performed low-pass whole genome bisulfite sequencing (WGBS) of 86 NDBS DNA to examine early life Down syndrome (DS) DNA methylation profiles. DS represents an example of genetics shaping epigenetics, as multiple array-based studies have demonstrated that trisomy 21 is characterized by genome-wide alterations to DNA methylation. By assaying over 24 million CpG sites, thousands of genome-wide significant (q < 0.05) differentially methylated regions (DMRs) that distinguished DS from typical development and idiopathic developmental delay were identified. Machine learning feature selection refined these DMRs to 22 loci. The DS DMRs mapped to genes involved in neurodevelopment, metabolism, and transcriptional regulation. Based on comparisons with previous DS methylation studies and reference epigenomes, the hypermethylated DS DMRs were significantly (q < 0.05) enriched across tissues while the hypomethylated DS DMRs were significantly (q < 0.05) enriched for blood-specific chromatin states. A ~28 kb block of hypermethylation was observed on chromosome 21 in the RUNX1 locus, which encodes a hematopoietic transcription factor whose binding motif was the most significantly enriched (q < 0.05) overall and specifically within the hypomethylated DMRs. Finally, we also identified DMRs that distinguished DS NDBS based on the presence or absence of congenital heart disease (CHD). Together, these results not only demonstrate the utility of low-pass WGBS on NDBS samples for epigenome-wide association studies, but also provide new insights into the early life mechanisms of epigenomic dysregulation resulting from trisomy 21.

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Active BRAF-V600E is the key player in generation of a sessile serrated polyp-specific DNA methylation profile

PLoS ONE ◽

10.1371/journal.pone.0192499 ◽

2018 ◽

Vol 13 (3) ◽

pp. e0192499 ◽

Cited By ~ 4

Author(s):

Somaye Dehghanizadeh ◽

Vahid Khoddami ◽

Timothy L. Mosbruger ◽

Sue S. Hammoud ◽

Kornelia Edes ◽

...

Keyword(s):

Dna Methylation ◽

Methylation Profile ◽

Braf V600e ◽

Serrated Polyp ◽

Dna Methylation Profile

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Methylome and transcriptome analyses of soybean response to bean pyralid larvae

BMC Genomics ◽

10.1186/s12864-021-08140-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Wei-Ying Zeng ◽

Yu-Rong Tan ◽

Sheng-Feng Long ◽

Zu-Dong Sun ◽

Zhen-Guang Lai ◽

...

Keyword(s):

Dna Methylation ◽

Protein Biosynthesis ◽

Cell Structure ◽

Methylation Profile ◽

Primary Metabolism ◽

Global Methylation ◽

Genome Wide ◽

Differentially Methylated Genes ◽

Dna Methylation Profile ◽

Soybean Resistance

Abstract Background Bean pyralid is one of the major leaf-feeding insects that affect soybean crops. DNA methylation can control the networks of gene expressions, and it plays an important role in responses to biotic stress. However, at present the genome-wide DNA methylation profile of the soybean resistance to bean pyralid has not been reported so far. Results Using whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq), we analyzed the highly resistant material (Gantai-2-2, HRK) and highly susceptible material (Wan82–178, HSK), under bean pyralid larvae feeding 0 h and 48 h, to clarify the molecular mechanism of the soybean resistance and explore its insect-resistant genes. We identified 2194, 6872, 39,704 and 40,018 differentially methylated regions (DMRs), as well as 497, 1594, 9596 and 9554 differentially methylated genes (DMGs) in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48 comparisons, respectively. Through the analysis of global methylation and transcription, 265 differentially expressed genes (DEGs) were negatively correlated with DMGs, there were 34, 49, 141 and 116 negatively correlated genes in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48, respectively. The MapMan cluster analysis showed that 114 negatively correlated genes were clustered in 24 pathways, such as protein biosynthesis and modification; primary metabolism; secondary metabolism; cell cycle, cell structure and component; RNA biosynthesis and processing, and so on. Moreover, CRK40; CRK62; STK; MAPK9; L-type lectin-domain containing receptor kinase VIII.2; CesA; CSI1; fimbrin-1; KIN-14B; KIN-14 N; KIN-4A; cytochrome P450 81E8; BEE1; ERF; bHLH25; bHLH79; GATA26, were likely regulatory genes involved in the soybean responses to bean pyralid larvae. Finally, 5 DMRs were further validated that the genome-wide DNA data were reliable through PS-PCR and 5 DEGs were confirmed the relationship between DNA methylation and gene expression by qRT-PCR. The results showed an excellent agreement with deep sequencing. Conclusions Genome-wide DNA methylation profile of soybean response to bean pyralid was obtained for the first time. Several specific DMGs which participated in protein kinase, cell and organelle, flavonoid biosynthesis and transcription factor were further identified to be likely associated with soybean response to bean pyralid. Our data will provide better understanding of DNA methylation alteration and their potential role in soybean insect resistance.

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