1887

Abstract

Abstract

Increasing evidence suggests that environmental exposures during in utero development impact adult health through epigenetic modifications of the genome. High production-volume chemicals such as bisphenol A (BPA), and known toxins including lead (Pb), are ubiquitous in the environment and may contribute to disease susceptibility through epigenetic mechanisms. Developmental and adult exposure to environmentally relevant levels of BPA has been shown to affect both global and gene-specific DNA methylation patterns. Preliminary studies also indicate that Pb exhibits epigenetic effects that may contribute to its known neurotoxic and obesogenic activities. During early embryogenesis, epigenetic marks, including DNA methylation, are reset at specific times in both rodents and humans. Utilizing the viable yellow agouti (Avy) mouse as a biosensor, we assess the impact of BPA and Pb on the DNA methylation status of the genome by examining coat color shifts, whole genome methylation, and repetitive element methylation. Since repetitive elements comprise nearly half of the human genome and contribute to disease when reactivated, the suppressive methylation of these elements during development is crucial to human health outcomes. Previously, only a handful of repetitive elements were known to be epigenetically variable; here we describe additional novel and environmentally responsive epigenetic elements. To illustrate the long-term biological dysregulation caused by BPA and Pb, we survey the epigenomic changes on repetitive elements and the whole genome induced by developmental exposure in mice as well as humans. The characterization of epialleles in the mouse, the most widely used model for human health, is crucial for the identification of human epialleles and the development of epigenetic therapies for the prevention and treatment of human disease throughout the life course.

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/content/papers/10.5339/qproc.2012.mutagens.3.35
2012-03-01
2019-10-15
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http://instance.metastore.ingenta.com/content/papers/10.5339/qproc.2012.mutagens.3.35
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  • Received: 09 May 2012
  • Accepted: 09 May 2012
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