Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health

Tsai, Pei-Chien; Glastonbury, Craig A.; Eliot, Melissa; Bollepalli, Sailalitha; Yet, İdil; Castillo-Fernandez, Juan; Carnero‐Montoro, Elena; Hardiman, Thomas; Martin, Tiphaine; Vickers, Alice; Mangino, Massimo; Ward, Kirsten; PietilaÌˆinen, K. H.; Deloukas, Panos; Spector, Tim D.; Viñuela, Ana; Loucks, Eric B.; Ollikainen, Miina; Kelsey, Karl T.; Small, Kerrin S.; Bell, Jordana T.

doi:10.1101/353581

Cited by 4 publications

(6 citation statements)

References 86 publications

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“…Additionally, three CpG sites within CYP1A1 and RNF122 were identified in both meta-analyses but with different directions of association in cord blood versus placenta. Interestingly, we observed CYP1A1 to be hypomethylated in placenta with exposure to MSDP, which is consistent with studies of adipose, skin, and lung tissues 54 , but this CpG was hypermethylated in the cord blood meta-analysis 10 . Additionally, the most statistically significant association with MSDP in placenta (cg27402634, LEKR1 ) was not associated with MSDP in the cord blood meta-analysis.…”

Section: Discussionsupporting

confidence: 90%

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Everson

Vives-Usano

Seyve

et al. 2019

Preprint

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Section: Discussionsupporting

confidence: 90%

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Everson

Vives-Usano

Seyve

et al. 2019

Preprint

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“…In other words, DNA methylation response to maternal smoking in pregnancy was not mirrored at the transcriptional level of nearby genes. Similarly, previous studies in former smokers have shown that smoking has a longer-lasting influence on the methylome compared to the transcriptome [67]. The reversal rate of gene expression at 1 year after smoking cessation has been calculated in > 50% and reaches > 85% after 10 years, whereas for methylation, it ranges from 17 to 33% with some effects still visible 40 years after smoking cessation.…”

Section: Discussionsupporting

confidence: 56%

In utero and childhood exposure to tobacco smoke and multi-layer molecular signatures in children

Vives-Usano

Hernández-Ferrer

Maitre

et al. 2020

BMC Med

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Background: The adverse health effects of early life exposure to tobacco smoking have been widely reported. In spite of this, the underlying molecular mechanisms of in utero and postnatal exposure to tobacco smoke are only partially understood. Here, we aimed to identify multi-layer molecular signatures associated with exposure to tobacco smoke in these two exposure windows. Methods: We investigated the associations of maternal smoking during pregnancy and childhood secondhand smoke (SHS) exposure with molecular features measured in 1203 European children (mean age 8.1 years) from the Human Early Life Exposome (HELIX) project. Molecular features, covering 4 layers, included blood DNA methylation and gene and miRNA transcription, plasma proteins, and sera and urinary metabolites. Results: Maternal smoking during pregnancy was associated with DNA methylation changes at 18 loci in child blood. DNA methylation at 5 of these loci was related to expression of the nearby genes. However, the expression of these genes themselves was only weakly associated with maternal smoking. Conversely, childhood SHS was not associated with blood DNA methylation or transcription patterns, but with reduced levels of several serum metabolites and with increased plasma PAI1 (plasminogen activator inhibitor-1), a protein that inhibits fibrinolysis. Some of the in utero and childhood smoking-related molecular marks showed dose-response trends, with stronger effects with higher dose or longer duration of the exposure.

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“…The rapidly emerging literature shows the methylation alterations in the promoter regions of CYP1B1 in several tumors, including prostate cancer (Tokizane et al, 2005), acute lymphoblastic leukemia (DiNardo et al, 2013) and gastric carcinoma (Kang et al, 2008). Furthermore, hypo-methylated CYP1B1 was up-regulated in current smokers (Tsai et al, 2018). Therefore, silencing of CYP1B1 via promoter methylation by MECP2 overexpression might be another explanation for its protective effects against CSE-induced epithelial cell injury.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, bioinformatics analyses by Cao et al identified CYP1B1 as a potential target in smoking-mediating malignancies (Cao et al, 2015). Experimental analysis further demonstrated that hypo-methylated CYP1B1 was up-regulated in current smokers (Tsai et al, 2018). Overexpression of CYP1B1 is considered to be aggressive therapeutic target in advanced nonsmall cell lung cancer (Su et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of MECP2 attenuates cigarette smoke extracts induced lung epithelial cell injury by promoting CYP1B1 methylation

et al. 2020

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MECP2 (Methyl-CpG-binding protein 2) has been shown to have a critical role in regulating DNA methylation against smoke exposed lung injury. However, the biological function of MECP2 and the underlying molecular mechanism remains elusive. Human bronchial epithelial (16HBE) and alveolar type II epithelial cells (AECII) were exposed to increasing concentrations of cigarette smoke extracts (CSE) solution to establish CSE-induced lung epithelial cell injury models. Our findings revealed that MECP2 was down-regulated, while CYP1B1 was up-regulated in CSE-induced lung epithelial cell injury models by quantitative real time PCR, western blotting and immunofluorescence staining. Down-regulated CYP1B1 was ascribed to the demethylation of its promoter by methylation-specific PCR (MSP). The in vitro experiments further showed that MECP2 overexpression significantly attenuated CSE-triggered cell growth attenuation, cell cycle arrest, apoptosis and ROS generation in lung epithelial cells by CCK-8 and flow cytometry assays. In molecular level, we further demonstrated that MECP2 overexpression obviously suppressed the expression of CYP1B1 through enhancing DNA methylation. Therefore, our data suggest that MECP2 protects against CSE-induced lung epithelial cell injury possibly through down-regulating CYP1B1 expression via elevating its methylation status.

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Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health

Abstract: Abstract

Cited by 4 publications

References 86 publications

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

In utero and childhood exposure to tobacco smoke and multi-layer molecular signatures in children

Overexpression of MECP2 attenuates cigarette smoke extracts induced lung epithelial cell injury by promoting CYP1B1 methylation

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