The long (LINEs) and the short (SINEs) of it: altered methylation as a precursor to toxicity.
Although once thought of as "junk" DNA, the importance of interspersed elements in the genome has become increasingly appreciated in recent years. In a broad sense these are collectively referred to as transposable elements, which encompass both transposons and retrotransposons. The latter include long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs). Expression of these elements leads to genetic instability. Therefore, it is important that they remain transcriptionally silenced, and DNA methylation plays a key role in this regard. A framework for understanding the possible interplay between altered DNA methylation, an epigenetic change, and mutational events is presented. A case is made as to how retrotransposable elements, specifically LINEs and SINEs, are likely to emerge as key players in furthering our understanding of mechanisms underlying a variety of toxicities, including carcinogenesis but not limited to this endpoint.
Carnell
Ammie N
AN
Department of Pharmacology and Toxicology, Michigan State University, B-440 Life Science Building, East Lansing, Michigan 48824, USA.
Goodman
Jay I
JI
D000818:Animals; D019175:DNA Methylation / Q000187:drug effects*; D004251:DNA Transposable Elements / Q000187:drug effects / Q000235:genetics; D044127:Epigenesis, Genetic; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000187:drug effects* / Q000235:genetics; D009153:Mutagens / Q000633:toxicity*; D020086:Short Interspersed Nucleotide Elements / Q000187:drug effects* / Q000235:genetics; D015262:Xenobiotics / Q000633:toxicity*
D004251:DNA Transposable Elements; D009153:Mutagens; D015262:Xenobiotics