scholarly journals Association Between miR-148a and DNA Methylation Profile in Individuals Exposed to Lead (Pb)

2021 ◽  
Vol 12 ◽  
Author(s):  
Marília Ladeira de Araújo ◽  
Bruno Costa Gomes ◽  
Paula Pícoli Devóz ◽  
Nathália de Assis Aguilar Duarte ◽  
Diego Luis Ribeiro ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Status ◽  
Epidemiologic Studies ◽  
Methylation Profile ◽  
Taqman Assay ◽  
Inverse Association ◽  
Dna Methylation Profile ◽  
Lead Levels ◽  
Mirnas Expression ◽  
The Impact

Experimental and epidemiologic studies have shown that lead (Pb) is able to induce epigenetic modifications, such as changes in DNA methylation profiles, in chromatin remodeling, as well as the expression of non-coding RNAs (ncRNAs). However, very little is known about the interactions between microRNAs (miRNAs) expression and DNA methylation status in individuals exposed to the metal. The aim of the present study was to investigate the impact of hsa-miR-148a expression on DNA methylation status, in 85 workers exposed to Pb. Blood and plasma lead levels (BLL and PLL, respectively) were determined by ICP-MS; expression of the miRNA-148a was quantified by RT-qPCR (TaqMan assay) and assessment of the global DNA methylation profile (by measurement of 5-methylcytosine; % 5-mC) was performed by ELISA. An inverse association was seen between miR-148a and % 5-mC DNA, as a function of BLL and PLL (β = −3.7; p = 0.071 and β = −4.1; p = 0.049, respectively) adjusted for age, BMI, smoking, and alcohol consumption. Taken together, our study provides further evidence concerning the interactions between DNA methylation profile and miR-148a, in individuals exposed to Pb.

scholarly journals Early life adversity alters normal sex-dependent developmental dynamics of DNA methylation

2016 ◽  
Vol 28 (4pt2) ◽  
pp. 1259-1272 ◽  
Author(s):  
Renaud Massart ◽  
Zsofia Nemoda ◽  
Matthew J. Suderman ◽  
Sheila Sutti ◽  
Angela M. Ruggiero ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Life ◽  
Maternal Separation ◽  
Methylation Profile ◽  
Early Life Adversity ◽  
Developmental Evolution ◽  
Dna Methylation Profile ◽  
Males And Females ◽  
The Difference ◽  
The Impact

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.

scholarly journals Genome-wide DNA methylation analysis of Metarhizium anisopliae during tick mimicked infection condition

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Nicolau Sbaraini ◽  
Reinaldo Bellini ◽  
Augusto Bartz Penteriche ◽  
Rafael Lucas Muniz Guedes ◽  
Ane Wichine Acosta Garcia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Metarhizium Anisopliae ◽  
Methylation Profile ◽  
Virulence Determinants ◽  
Infection Cycle ◽  
Fungal Virulence ◽  
Genome Wide ◽  
Dna Methylation Profile ◽  
The Impact

Abstract Background The Metarhizium genus harbors important entomopathogenic fungi. These species have been widely explored as biological control agents, and strategies to improve the fungal virulence are under investigation. Thus, the interaction between Metarhizium species and susceptible hosts have been explored employing different methods in order to characterize putative virulence determinants. However, the impact of epigenetic modulation on the infection cycle of Metarhizium is still an open topic. Among the different epigenetic modifications, DNA methylation of cytosine bases is an important mechanism to control gene expression in several organisms. To better understand if DNA methylation can govern Metarhizium-host interactions, the genome-wide DNA methylation profile of Metarhizium anisopliae was explored in two conditions: tick mimicked infection and a saprophytic-like control. Results Using a genome wide DNA methylation profile based on bisulfite sequencing (BS-Seq), approximately 0.60% of the total cytosines were methylated in saprophytic-like condition, which was lower than the DNA methylation level (0.89%) in tick mimicked infection condition. A total of 670 mRNA genes were found to be putatively methylated, with 390 mRNA genes uniquely methylated in the tick mimicked infection condition. GO terms linked to response to stimuli, cell wall morphogenesis, cytoskeleton morphogenesis and secondary metabolism biosynthesis were over-represented in the tick mimicked infection condition, suggesting that energy metabolism is directed towards the regulation of genes associated with infection. However, recognized virulence determinants known to be expressed at distinct infection steps, such as the destruxin backbone gene and the collagen-like protein gene Mcl1, were found methylated, suggesting that a dynamic pattern of methylation could be found during the infectious process. These results were further endorsed employing RT-qPCR from cultures treated or not with the DNA methyltransferase inhibitor 5-Azacytidine. Conclusions The set of genes here analyzed focused on secondary metabolites associated genes, known to be involved in several processes, including virulence. The BS-Seq pipeline and RT-qPCR analysis employing 5-Azacytidine led to identification of methylated virulence genes in M. anisopliae. The results provided evidences that DNA methylation in M. anisopliae comprises another layer of gene expression regulation, suggesting a main role of DNA methylation regulating putative virulence determinants during M. anisopliae infection cycle.

Dysregulation of DNA Methylation Involves in Progression of Myeloid Leukemia in Down Syndrome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 89-89 ◽  
Author(s):  
Satoshi Saida ◽  
Masahiro Nakamura ◽  
Tsutomu Toki ◽  
Yoko Nishinaka-Arai ◽  
Kiminori Terui ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Down Syndrome ◽  
First Generation ◽  
Xenograft Model ◽  
Methylation Profile ◽  
Clinical Samples ◽  
Global Dna Methylation ◽  
Dna Methylation Profile ◽  
Malignant Conversion ◽  
The Impact

Abstract Transient abnormal myelopoiesis (TAM) is a clonal pre-leukemic disorder in neonates of Down syndrome. Although self-limiting in a majority of cases, TAM may evolve as non-self-limiting acute megakaryoblastic leukemia (DS-AMKL) after spontaneous remission. As such, the study of TAM/DS-AMKL can provide insight into the mechanisms of leukemic evolution. Our recent study has shown that DS-AMKL from TAM is shaped by acquisition of new mutations and clonal selection, and genomic mutations in epigenetic regulators frequently preceded other driver mutations. In this study, we address biological significance of the mutations in a progression from TAM to DS-AMKL using a newly established xenograft model of malignant conversion of the leukemia. We first analyzed global DNA methylation profile of clinical samples including 21 TAM and 10 DS-AMKL, using Infiniun 450K DNA methylation array (Illumina). Although averaged DNA methylation levels of both TAM and DS-AMKL were approximately the same, we observed two distinct clusters delineating TAM and DS-AMKL samples by both hierarchical clustering and principle component analysis (PCA). We identified differentially methylated cytosines on the promoters (TAM/AMKL-DMCpGs) between the two groups, and found that most of TAM/AMKL-DMCpGs were hyper-methylated in DS-AMKL samples compared to TAM, indicating that hyper-methylation of the subset of CpGs is a hallmark of DS-AMKL. To follow sequential alterations of DNA methylation profile, we established a xenograft model of the leukemia, which mimicked the progression of TAM to DS-AMKL. We transplanted TAM blast cells (1x106 cells) derived from the patient, who developed DS-AMKL later, into NOD/SCID/γc null (NOG) mice through tail vein. One series of the xenografts exhibited engraftment in the mouse and could passage by serial engraftment in vivo, whereas the other exhibited engraftment, but could not maintain in the mice by serial transplantation. The global DNA methylation profile of engrafted cells from the first generation mice was closed to TAM patients, whereas those from the forth, fifth and sixth generations approached to DS-AMKL patients. Moreover, hyper-methylation of TAM/AMKL-DMCpGs was also observed in engrafted TAM cells with higher numbers of passages, demonstrated that the xenograft model mimicked dysregulation of DNA methylation in disease progression of TAM. We further investigated the impact of dysregulation of DNA methylation on gene expression. As expected, RNA-seq and hierarchal clustering analyses of genes regulated by TAM/AMKL-DMCpGs displayed distinct two clusters, one with TAM samples and the first generation engraftments and another with DS-AMKL samples and 4th, 5th and 6th generation engraftments. We propose that epigenetic dysregulation is a crucial step for malignant conversion of TAM into DS-AMKL. Disclosures No relevant conflicts of interest to declare.

The DNA methylation profile of oocytes in mice with hyperinsulinaemia and hyperandrogenism as detected by single-cell level whole genome bisulphite sequencing (SC-WGBS) technology

2018 ◽  
Vol 30 (12) ◽  
pp. 1713 ◽  
Author(s):  
Qian-Nan Li ◽  
Lei Guo ◽  
Yi Hou ◽  
Xiang-Hong Ou ◽  
Zhonghua Liu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Single Cell ◽  
Familial Aggregation ◽  
Methylation Status ◽  
Methylation Profile ◽  
Whole Genome ◽  
Single Cell Level ◽  
Cell Level ◽  
Bisulphite Sequencing ◽  
Dna Methylation Profile

Polycystic ovary syndrome (PCOS), a familial aggregation disease that causes anovulation in women, has well-recognised characteristics, two of which are hyperinsulinaemia and hyperandrogenaemia. To determine whether the DNA methylation status is altered in oocytes by high insulin and androgen levels, we generated a mouse model with hyperinsulinaemia and hyperandrogenaemia by injection of insulin and human chorionic gonadotrophin and investigated DNA methylation changes through single-cell level whole genome bisulphite sequencing. Our results showed that hyperinsulinaemia and hyperandrogenaemia had no significant effects on the global DNA methylation profile and different functional regions of genes, but did alter methylation status of some genes, which were significantly enriched in 17 gene ontology (GO) terms (P < 0.05) by GO analysis. Among differently methylated genes, some were related to the occurrence of PCOS. Based on our results, we suggest that hyperinsulinaemia and hyperandrogenaemia may cause changes in some DNA methylation loci in oocytes.

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

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&lt;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

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

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.

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

Epigenetics ◽  
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

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

Placenta ◽  
2014 ◽  
Vol 35 (3) ◽  
pp. 216-222 ◽  
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

scholarly journals Genome-Wide DNA Methylation Pattern of Cancer Stem Cells in Esophageal Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382098379
Author(s):  
Xiying Yu ◽  
Ying Teng ◽  
Xingran Jiang ◽  
Hui Yuan ◽  
Wei Jiang
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Esophageal Cancer ◽  
Cancer Stem Cells ◽  
Side Population ◽  
Methylation Status ◽  
Methylation Profile ◽  
Cpg Dinucleotides ◽  
Genome Wide ◽  
Differentially Methylated Genes

Background: Cancer stem cells (CSCs) are considered the main cause of cancer recurrence and metastasis, and DNA methylation is involved in the maintenance of CSCs. However, the methylation profile of esophageal CSCs remains unknown. Methods: Side population (SP) cells were isolated from esophageal squamous cell carcinoma (ESCC) cell lines KYSE150 and EC109. Sphere-forming cells were collected from human primary esophageal cancer cells. SP cells and sphere-forming cells were used as substitutes for cancer stem-like cells. We investigated the genome-wide DNA methylation profile in esophageal cancer stem-like cells using reduced representation bisulfite sequencing (RRBS). Results: Methylated cytosine (mC) was found mostly in CpG dinucleotides, located mostly in the intronic, intergenic, and exonic regions. Forty intersected differentially methylated regions (DMRs) were identified in these 3 groups of samples. Thirteen differentially methylated genes with the same alteration trend were detected; these included OTX1, SPACA1, CD163L1, ST8SIA2, TECR, CADM3, GRM1, LRRK1, CHSY1, PROKR2, LINC00658, LOC100506688, and NKD2. DMRs covering ST8SIA2 and GRM1 were located in exons. These differentially methylated genes were involved in 10 categories of biological processes and 3 cell signaling pathways. Conclusions: When compared to non-CSCs, cancer stem-like cells have a differential methylation status, which provides an important biological base for understanding esophageal CSCs and developing therapeutic targets for esophageal cancer.

Sign in / Sign up

Export Citation Format

Share Document