Cigarette smoking and DNA methylation

Abstract

DNA methylation is the most studied epigenetic modification, capable of controlling gene expression in the contexts of normal traits or diseases. It is highly dynamic during early embryogenesis and remains relatively stable throughout life, and such patterns are intricately related to human development. DNA methylation is a quantitative trait determined by a complex interplay of genetic and environmental factors. Genetic variants at a specific locus can influence both regional and distant DNA methylation. The environment can have varying effects on DNA methylation depending on when the exposure occurs, such as during prenatal life or during adulthood. In particular, cigarette smoking in the context of both current smoking and prenatal exposure is a strong modifier of DNA methylation. Epigenome-wide association studies have uncovered candidate genes associated with cigarette smoking that have biologically relevant functions in the etiology of smoking-related diseases. As such, DNA methylation is a potential mechanistic link between current smoking and cancer, as well as prenatal cigarette-smoke exposure and the development of adult chronic diseases.

Keywords: DNA methylation; cigarette smoking; epigenetics; epigenome; prenatal exposure.

FIGURE 1

DNA methylation during development and aging. The changes in the human methylome can be divided into three stages: (1) transition from zygote to pre-implantation blastocyst, (2) transition from implanted blastocyst to early fetal development, and (3) transition into adult life. Genes and the environment (4) influence DNA methylation patterns at each of these stages.

FIGURE 2

Effects of cigarette smoke exposure on DNA methylation. Cigarette smoke has been shown to modulate DNA methyltransferase 1 (DNMT1) content, both at the transcript and protein level, and enzymatic activity separately in different cell types. Double-stranded DNA breaks may be induced by cigarette smoke, which subsequently recruits DNMT1 adjacent to the repair site. DNA-binding proteins, such as Sp1, are activated by cigarette smoke and protect CpG sites from de novo methylation. In the context of prenatal exposure, cigarette smoke induces hypoxia in the embryo, which in turn modulates methyl group availability.