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ToxSci Advance Access originally published online on May 28, 2003
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Toxicological Sciences 75, 229-235 (2003)
Copyright © 2003 by the Society of Toxicology

REVIEW

The Long (LINEs) and the Short (SINEs) of It: Altered Methylation as a Precursor to Toxicity

Ammie N. Carnell and Jay I. Goodman1

Department of Pharmacology and Toxicology, Michigan State University, B-440 Life Science Building, East Lansing, Michigan 48824

ABSTRACT

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.

Key Words: DNA methylation; epigenetics; LINEs, retrotransposons; transposable elements; SINEs.


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