scholarly journals Sex-specific DNA methylation differences in people exposed to polybrominated biphenyl

Epigenomics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 757-770
Author(s):  
Sarah W Curtis ◽  
Sabrina A Gerkowicz ◽  
Dawayland O Cobb ◽  
Varun Kilaru ◽  
Metrecia L Terrell ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Health Risks ◽  
Binding Sites ◽  
Adverse Health Outcomes ◽  
Functional Regions ◽  
Specific Effects ◽  
False Discovery ◽  
Polybrominated Biphenyls ◽  
Polybrominated Biphenyl ◽  
Specific Health

Aim: Michigan residents were exposed to polybrominated biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate <0.05). No CpGs were associated in both sexes. These CpGs were enriched in different functional regions and transcription factor binding sites in each sex. Conclusion: Exposure to PBBs may have sex-specific effects on the epigenome that may underlie sex-specific adverse health outcomes.

scholarly journals Grandmaternal smoking during pregnancy is associated with differential DNA methylation in their grandchildren

2021 ◽  
Author(s):  
Sarah Holmes Watkins ◽  
Yasmin Iles-Caven ◽  
Marcus Pembrey ◽  
Jean Golding ◽  
Matthew Suderman
Keyword(s):  
Dna Methylation ◽  
Binding Sites ◽  
Association Studies ◽  
Epidemiological Studies ◽  
Limited Evidence ◽  
Smoking During Pregnancy ◽  
Cpg Sites ◽  
Specific Effects ◽  
Imprinting Control Region ◽  
First Time

AbstractThe idea that information can be transmitted to subsequent generation(s) by epigenetic means has been studied for decades but remains controversial in humans. Epidemiological studies have established that grandparental exposures are associated with health outcomes in their grandchildren, often with sex-specific effects; however the mechanism of transmission is still unclear. We conducted Epigenome Wide Association Studies (EWAS) to test whether grandmaternal smoking during pregnancy is associated with altered DNA methylation (DNAm) in their adolescent grandchildren. We used data from a birth cohort, with discovery and replication datasets of 1225 and 708 individuals (respectively), aged 15-17 years, and tested replication in the same individuals at birth and 7 years. We show for the first time that DNAm at a small number of loci is associated with grandmaternal smoking in humans, and their locations in the genome suggest hypotheses of transmission. We observe and replicate sex-specific associations at two sites on the X chromosome, one located in an imprinting control region and both within transcription factor binding sites (TFBSs). In fact, we observe enrichment for TFBSs among the CpG sites with the strongest associations, suggesting that TFBSs may be a mechanism by which grandmaternal exposures influence offspring DNA methylation. There is limited evidence that these associations appear at earlier timepoints, so effects are not static throughout development. The implication of this work is that effects of smoking during pregnancy may induce DNAm changes in later generations and that these changes are often sex-specific, in line with observational associations.

scholarly journals Birthweight DNA methylation signatures in infant saliva

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chiara Moccia ◽  
Maja Popovic ◽  
Elena Isaevska ◽  
Valentina Fiano ◽  
Morena Trevisan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Gestational Age ◽  
Low Birthweight ◽  
Continuous Variable ◽  
Linear Regression Models ◽  
Association Analyses ◽  
Cpg Sites ◽  
Adverse Health Outcomes ◽  
The Look

Abstract Background Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to look-up cord blood birthweight-associated CpG sites identified by the PACE Consortium in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight. Methods DNA methylation was assessed using Infinium HumanMethylation450K array in 135 saliva samples collected from children of the NINFEA birth cohort at an average age of 10.8 (range 7–17) months. The association analyses between birthweight and DNA methylation variations were carried out using robust linear regression models both in the exploratory EWAS analyses and in the look-up of the PACE findings in infant saliva. Results None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was associated with birthweight when analysed in infant saliva. In saliva EWAS analyses, considering a false discovery rate p-values < 0.05, birthweight as continuous variable was associated with DNA methylation in 44 CpG sites; being born small for gestational age (SGA, lower 10th percentile of birthweight for gestational age according to WHO reference charts) was associated with DNA methylation in 44 CpGs, with only one overlapping CpG between the two analyses. Despite no overlap with PACE results at the CpG level, two of the top saliva birthweight CpGs mapped at genes associated with birthweight with the same direction of the effect also in the PACE Consortium (MACROD1 and RPTOR). Conclusion Our study provides an indication of the birthweight and SGA epigenetic salivary signatures in children around 10 months of age. DNA methylation signatures in cord blood may not be comparable with saliva DNA methylation signatures at about 10 months of age, suggesting that the birthweight epigenetic marks are likely time and tissue specific.

scholarly journals Trichloroethylene-induced alterations in DNA methylation were enriched in polycomb protein binding sites in effector/memory CD4+ T cells

2017 ◽  
Vol 3 (3) ◽  
Author(s):  
Kathleen M. Gilbert ◽  
Sarah J. Blossom ◽  
Brad Reisfeld ◽  
Stephen W. Erickson ◽  
Kanan Vyas ◽  
...  
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
Protein Binding ◽  
Binding Sites ◽  
Cd4 T Cells ◽  
Effector Memory ◽  
Protein Binding Sites ◽  
Polycomb Protein ◽  
Memory Cd4 T Cells

Impact of depression and stress on placental DNA methylation in ethnically diverse pregnant women

Epigenomics ◽  
2021 ◽  
Author(s):  
Markos Tesfaye ◽  
Suvo Chatterjee ◽  
Xuehuo Zeng ◽  
Paule Joseph ◽  
Fasil Tekola-Ayele
Keyword(s):  
Dna Methylation ◽  
Fetal Brain ◽  
Ethnically Diverse ◽  
Antenatal Depression ◽  
Epigenetic Changes ◽  
Clinical Trial Registration ◽  
False Discovery ◽  
Genome Wide ◽  
Neuropsychiatric Diseases ◽  
Registration Number

Aim: To investigate the association between placental genome-wide methylation at birth and antenatal depression and stress during pregnancy. Methods: We examined the association between placental genome-wide DNA methylation (n = 301) and maternal depression and stress assessed at six gestation periods during pregnancy. Correlation between DNA methylation at the significantly associated CpGs and expression of nearby genes in the placenta was tested. Results: Depression and stress were associated with methylation of 16 CpGs and two CpGs, respectively, at a 5% false discovery rate. Methylation levels at two of the CpGs associated with depression were significantly associated with expression of ADAM23 and CTDP1, genes implicated in neurodevelopment and neuropsychiatric diseases. Conclusion: Placental epigenetic changes linked to antenatal depression suggest potential fetal brain programming. Clinical trial registration number: NCT00912132 (ClinicalTrials.gov)

scholarly journals DNA methylation changes are a late event in acute promyelocytic leukemia and coincide with loss of transcription factor binding

Blood ◽  
2013 ◽  
Vol 121 (1) ◽  
pp. 178-187 ◽  
Author(s):  
Till Schoofs ◽  
Christian Rohde ◽  
Katja Hebestreit ◽  
Hans-Ulrich Klein ◽  
Stefanie Göllner ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transcription Factor ◽  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Binding Sites ◽  
Embryonic Stem ◽  
Transcription Factor Binding ◽  
Promyelocytic Leukemia ◽  
Factor Binding ◽  
Aberrant Dna Methylation

Abstract The origin of aberrant DNA methylation in cancer remains largely unknown. In the present study, we elucidated the DNA methylome in primary acute promyelocytic leukemia (APL) and the role of promyelocytic leukemia–retinoic acid receptor α (PML-RARα) in establishing these patterns. Cells from APL patients showed increased genome-wide DNA methylation with higher variability than healthy CD34+ cells, promyelocytes, and remission BM cells. A core set of differentially methylated regions in APL was identified. Age at diagnosis, Sanz score, and Flt3-mutation status characterized methylation subtypes. Transcription factor–binding sites (eg, the c-myc–binding sites) were associated with low methylation. However, SUZ12- and REST-binding sites identified in embryonic stem cells were preferentially DNA hypermethylated in APL cells. Unexpectedly, PML-RARα–binding sites were also protected from aberrant DNA methylation in APL cells. Consistent with this, myeloid cells from preleukemic PML-RARα knock-in mice did not show altered DNA methylation and the expression of PML-RARα in hematopoietic progenitor cells prevented differentiation without affecting DNA methylation. Treatment of APL blasts with all-trans retinoic acid also did not result in immediate DNA methylation changes. The results of the present study suggest that aberrant DNA methylation is associated with leukemia phenotype but is not required for PML-RARα–mediated initiation of leukemogenesis.

scholarly journals Prediction of smoking by multiplex bisulfite PCR with long amplicons considering allele-specific effects on DNA methylation

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Nikolay Kondratyev ◽  
Arkady Golov ◽  
Margarita Alfimova ◽  
Tatiana Lezheiko ◽  
Vera Golimbet
Keyword(s):  
Dna Methylation ◽  
Specific Effects ◽  
Allele Specific

scholarly journals The interplay between DNA methylation and sequence divergence in recent human evolution

2015 ◽  
Author(s):  
Irene Hernando-Herraez ◽  
Holger Heyn ◽  
Marcos Fernandez-Callejo ◽  
Enrique Vidal ◽  
Hugo Fernandez-Bellon ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transcription Factor ◽  
Binding Sites ◽  
Incomplete Lineage Sorting ◽  
Epigenetic Modification ◽  
Transcription Factor Binding Sites ◽  
Transcription Factor Binding ◽  
Factor Binding ◽  
Methylation Patterns ◽  
Human Specific

DNA methylation is a key regulatory mechanism in mammalian genomes. Despite the increasing knowledge about this epigenetic modification, the understanding of human epigenome evolution is in its infancy. We used whole genome bisulfite sequencing to study DNA methylation and nucleotide divergence between human and great apes. We identified 360 and 210 differentially hypo- and hypermethylated regions (DMRs) in humans compared to non-human primates and estimated that 20% and 36% of these regions, respectively, were detectable throughout several human tissues. Human DMRs were enriched for specific histone modifications and contrary to expectations, the majority were located distal to transcription start sites, highlighting the importance of regions outside the direct regulatory context. We also found a significant excess of endogenous retrovirus elements in human-specific hypomethylated regions suggesting their association with local epigenetic changes. We also reported for the first time a close interplay between inter-species genetic and epigenetic variation in regions of incomplete lineage sorting, transcription factor binding sites and human differentially hypermethylated regions. Specifically, we observed an excess of human-specific substitutions in transcription factor binding sites located within human DMRs, suggesting that alteration of regulatory motifs underlies some human-specific methylation patterns. We also found that the acquisition of DNA hypermethylation in the human lineage is frequently coupled with a rapid evolution at nucleotide level in the neighborhood of these CpG sites. Taken together, our results reveal new insights into the mechanistic basis of human-specific DNA methylation patterns and the interpretation of inter-species non-coding variation.

Determination of Polybrominated Biphenyl Residues in Dairy Products

1975 ◽  
Vol 58 (5) ◽  
pp. 978-982
Author(s):  
Norbert V Fehringer
Keyword(s):  
Dairy Products ◽  
Gel Permeation Chromatography ◽  
Fatty Material ◽  
Polybrominated Biphenyls ◽  
Gel Permeation ◽  
Aoac Method ◽  
Residue Levels ◽  
Polybrominated Biphenyl ◽  
Liquid Chromatographic

Abstract A method for the determination of polybrominated biphenyls (PBBs) in dairy products is described. Fat is extracted from the products by the official AOAC method. The PBB residues are separated from the fatty material by gel permeation chromatography prior to gas-liquid chromatographic (GLC) quantitation. An additional cleanup using petroleum ether elution through a miniature Florisil column is necessary for thin layer chromatographic (TLC) confirmation. Recoveries of PBBs from samples fortified at levels from 0.1 to 0.5 ppm ranged from 94 to 104% with an average of 99%. GLC sensitivity permits the estimation of PBB residue levels as low as 0.007 ppm. Routine TLC confirmation is limited by sensitivity to ≥0.2 ppm.

Determination of Polybrominated Biphenyl Residues in Dry Animal Feeds

1975 ◽  
Vol 58 (6) ◽  
pp. 1206-1210
Author(s):  
Norbert V Fehringer
Keyword(s):  
Petroleum Ether ◽  
Pesticide Residues ◽  
Methylene Chloride ◽  
Chromatographic Column ◽  
Animal Feeds ◽  
Polybrominated Biphenyls ◽  
Polybrominated Biphenyl ◽  
Liquid Chromatographic

Abstract A new procedure is described for the determination of polybrominated biphenyls (PBBs) in dry animal feeds and developmental results are discussed. Finely ground feed is packed into a chromatographic column containing Celite and then eluted with methylene chloride. The concentrated extract is cleaned up by elution with petroleum ether through Florisil before gas-liquid chromatographic quantitation. Chromatograms thus obtained were essentially free of the interfering peaks encountered when using AOAC methods for pesticide residues in dry products. Results of feed analyses by the proposed procedure averaged 30% higher than those obtained by AOAC procedures. Recoveries of PBBs from samples fortified at levels of 0.04 to 0.4 ppm ranged from 90 to 104%, with an average of 98%.

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