Epigenomic biomonitors: global DNA hypomethylation as a biodosimeter of life-long environmental exposures

Epigenomics refers to the study of genome-wide heritable changes in gene activity and expression in the progeny of cells or individuals, without a change in nucleotide sequence, and its contribution to cellular growth and differentiation, disease and aging. Epigenomics provides a window through which we can understand the exposome [1], that is the life-course impact of environment, nutrition and lifestyle choices on health and disease susceptibility, as well as risk [2]. Epigenomic processes, a whole-genome concert of heritable epigenetic changes acting with choreographed precision, behave in a cell-specific, temporally regulated fashion to direct normal development, differentiation, organogenesis, tissue formation, tissue maintenance and aging [3]. While genetic processes rely on the nucleotide sequence of the DNA, epigenomic processes depend on reversible biochemical alterations of the DNA strands or higher order chromatin packaging to regulate gene activity and expression. As such, epigenomic processes can be both appealing and elusive targets for biomonitoring environmental exposures. Epigenomic mechanisms are linked to gene activation, gene silencing and chromosomal instability, but questions still remain regarding the timing, maintenance and stability of epigenomic marks. Additional knowledge of how critical epigenomic patterns are inherited and maintained is needed to understand the role of the human epigenome in health and disease. For example, little is known regarding how normal growth and development are impacted by the epigenome, which is not a stable entity but rather highly dynamic, as it responds to micro- and macro-environments throughout the life course [4]. Epigenomic changes are tissue, exposure or disease specific and seem to be in a dynamic flux during the cell cycle and in mitotic divisions [5]. The epigenome is linked to circadian rhythms, is highly dependent on lifestyle and context and may be associated with maternal and grand-maternal exposures. As such, it is a magnificent molecular tapestry of ourselves, providing a record of where we come from and a roadmap of who we will become – invaluable information pending our ability to decipher it. Furthermore, because of its potentially modifiable, yet fundamentally stable nature, there in lies the possibility that we might learn how to manipulate the epigenome to nurture and promote health, as well as to prevent or treat disease [6].