Response of transposable elements to environmental stressors

Abstract

Transposable elements (TEs) comprise a group of repetitive sequences that bring positive, negative, as well as neutral effects to the host organism. Earlier considered as “junk DNA,” TEs are now well-accepted driving forces of evolution and critical regulators the of expression of genetic information. Their activity is regulated by epigenetic mechanisms, including methylation of DNA and histone modifications. The loss of epigenetic control over TEs, exhibited as loss of DNA methylation and decondensation of the chromatin structure, may result in TEs reactivation, initiation of their insertional mutagenesis (retrotransposition) and has been reported in numerous human diseases, including cancer. Accumulating evidence suggests that these alterations are not the simple consequences of the disease, but often may drive the pathogenesis, as they can be detected early during disease development. Knowledge derived from the in vitro, in vivo, and epidemiological studies, clearly demonstrates that exposure to ubiquitous environmental stressors, many of which are carcinogens or suspected carcinogens, are capable of causing alterations in methylation and expression of TEs and initiate retrotransposition events. Evidence summarized in this review suggests that TEs are the sensitive endpoints for detection of effects caused by such environmental stressors, as ionizing radiation (terrestrial, space, and UV-radiation), air pollution (including particulate matter [PM]-derived and gaseous), persistent organic pollutants, and metals. Furthermore, the significance of these effects is characterized by their early appearance, persistence and presence in both, target organs and peripheral blood. Altogether, these findings suggest that TEs may potentially be introduced into safety and risk assessment and serve as biomarkers of exposure to environmental stressors. Furthermore, TEs also show significant potential to become invaluable surrogate biomarkers in clinic and possible targets for therapeutic modalities for disease treatment and prevention.

Transcriptomic responses of the endangered freshwater mussel Margaritifera margaritifera to trace metal contamination in the Dronne River, France

“…In several cancer cell lines, the reduction of LINE-1-derived RT was found to reduce proliferation, promote differentiation, and reprogram the global transcription profiles of coding and non-coding sequences. In spite of the abundance and the putative role of transposable elements in shaping genome variation in bivalves (Zhang et al 2012), their response to environmental stressors remains poorly understood (Casacuberta and González 2013;Miousse et al 2015). The expression of retrotransposable elements usually increases with age; however, it could be reduced by caloric restriction (De Cecco et al 2013), and previous studies, though in marine mussels, showed that feeding rates are reduced with age (Bellas et al 2014).…”

Radiation-induced changes in DNA methylation of repetitive elements in the mouse heart

“…They are the most highly methylated sequences in mammalian genomes, and are represented as transposable elements and satellite repeats [1,7]. Retrotransposons, such as Long Interspersed Nucleotide Element 1 (LINE-1), Endogenous Retroviruses 1 and 2 (ERV1 and ERV2) and Short Interspersed Nucleotide Elements B1 and B2 (SINE B1 and SINE B2), as well as the transposons Mariner and Charlie are among the most abundant transposable elements in mammalian genomes and together comprise ~40% of the mouse genome [8]. Satellite repeats are the centromere-associated repetitive sequences and are represented in the mouse as major satellites (6 Mb of 234 bp units located primarily at the pericentromeric regions) and minor satellites (~600 Kb of 120 bp units, located at centromeres) [9].…”

2017 Michael Fry Award Lecture When DNA is Actually Not a Target: Radiation Epigenetics as a Tool to Understand and Control Cellular Response to Ionizing Radiation

“…Indeed, REs shape about 50% of mammalian genomes, with some computational studies estimating up to two-thirds of the genome to be represented as REs (17, 18). Since the REs are primarily transposons and retrotranspo-sons by nature, during the evolutionary arm race with the host, they were silenced by methylation of DNA to control their expression and potential (retro)transposition (11, 17, 19). …”

“…The DNA methylation capacity of this retrotransposon is tremendous, as LINE-1 comprises ~20% of mammalian genomes, roughly 10 times more than the entire protein-coding genes (17, 20). The full-length LINE-1 is comprised of the two open reading frames (ORF-1 and ORF-2), a 3′ untranslated region (UTR) and a CpG-reach 5′-UTR.…”