scholarly journals Maternal cigarette smoking affects DNA methylation in imprinting control regions and enhancer regions in placenta

2019 ◽  
Vol 3 ◽  
pp. 232
Author(s):  
Lepeule J ◽  
Seyve E ◽  
Chuffart F ◽  
Bourova-Flin E ◽  
Charles M ◽  
...  
Epigenetics ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Parisa Tehranifar ◽  
Hui-Chen Wu ◽  
Jasmine A. McDonald ◽  
Farzana Jasmine ◽  
Regina M. Santella ◽  
...  

2019 ◽  
Author(s):  
Sophie Rousseaux ◽  
Emie Seyve ◽  
Florent Chuffart ◽  
Ekaterina Bourova-Flin ◽  
Meriem Benmerad ◽  
...  

AbstractObjectiveExposure to cigarette smoking during pregnancy has been robustly associated with cord blood DNA methylation. However, little is known about such effects on the placenta; in particular, whether cigarette smoking before pregnancy could also induce epigenetic alterations in the placenta of former smokers is unknown.Design and resultsPlacental DNA methylation levels were measured in 568 women and compared among non-smokers and women either smoking during their pregnancy or who had ceased smoking before pregnancy. An Epigenome Wide Association Study identified 344 Differentially Methylated Regions (DMRs) significantly associated with maternal smoking status. Among these 344 DMRs, 262 showed “reversible” alterations of DNA methylation, only present in the placenta of current smokers, whereas 44 were also found altered in former smokers, whose placenta had not been exposed directly to cigarette smoking. This observation was further supported by a significant demethylation of LINE-1 sequences in the placentas of both current (−0.43 (−0.83 to −0.02)) and former smokers (−0.55 (−1.02 to −0.08)) compared to nonsmokers. A comparative analysis of the epigenome landscape based on the ENCODE placenta data demonstrated an enrichment of all 344 DMRs in enhancers histone marks. Additionally, smoking-associated DMRs were found near and/or overlapping with 13 imprinting gene clusters encompassing 18 imprinted genes.ConclusionsDNA methylation patterns alterations were found in 344 genomic regions in the placenta of women smoking during their pregnancy, including 44 DMRs and LINE-1 elements, where methylation changes persisted in former smokers, supporting the hypothesis of an “epigenetic memory” of exposure to cigarette smoking before pregnancy. Enhancers regions, including imprinting control regions were also particularly affected by placenta methylation changes associated to smoking, suggesting a biological basis for the sensitivity of these regions to tobacco exposure and mechanisms by which fetal development could be impacted.


2018 ◽  
Vol 57 ◽  
pp. 19-27 ◽  
Author(s):  
Svetlana Fa ◽  
Trine Vilsbøll Larsen ◽  
Katrine Bilde ◽  
Tina F. Daugaard ◽  
Emil H. Ernst ◽  
...  

2016 ◽  
Vol 8 (1) ◽  
Author(s):  
Svetlana Fa ◽  
Trine Vilsbøll Larsen ◽  
Katrine Bilde ◽  
Tina F. Daugaard ◽  
Emil H. Ernst ◽  
...  

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chen Yao ◽  
Roby Joehanes ◽  
Rory Wilson ◽  
Toshiko Tanaka ◽  
Luigi Ferrucci ◽  
...  

Abstract Background DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases. Results We performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data. Conclusions Our results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation.


Sign in / Sign up

Export Citation Format

Share Document