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Open AccessArticle

Imprinted Genes and the Environment: Links to the Toxic Metals Arsenic, Cadmium and Lead

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Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina, 135 Dauer Drive, CB 7431, UNC, Chapel Hill, NC 27599, USA
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Lineberger Comprehensive Cancer Center, The University of North Carolina, 450 West Street, CB 7295, UNC, Chapel Hill, NC 27599, USA
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Department of Obstetrics and Gynecology, Duke University Medical Center, B226 LSRC, Box 91012, Research Drive, Durham, NC 27708, USA
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Department of Biological Sciences, Center for Human Health and Environment, Campus Box 7633, NC State University, Raleigh, NC 27695, USA
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Curriculum in Toxicology, The University of North Carolina, 135 Dauer Drive, CB 7431, UNC, Chapel Hill, NC 27599, USA
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Author to whom correspondence should be addressed.
Genes 2014, 5(2), 477-496; https://doi.org/10.3390/genes5020477
Received: 8 April 2014 / Revised: 24 May 2014 / Accepted: 27 May 2014 / Published: 11 June 2014
(This article belongs to the Special Issue Grand Celebration: 10th Anniversary of the Human Genome Project)
Imprinted genes defy rules of Mendelian genetics with their expression tied to the parent from whom each allele was inherited. They are known to play a role in various diseases/disorders including fetal growth disruption, lower birth weight, obesity, and cancer. There is increasing interest in understanding their influence on environmentally-induced disease. The environment can be thought of broadly as including chemicals present in air, water and soil, as well as food. According to the Agency for Toxic Substances and Disease Registry (ATSDR), some of the highest ranking environmental chemicals of concern include metals/metalloids such as arsenic, cadmium, lead and mercury. The complex relationships between toxic metal exposure, imprinted gene regulation/expression and health outcomes are understudied. Herein we examine trends in imprinted gene biology, including an assessment of the imprinted genes and their known functional roles in the cell, particularly as they relate to toxic metals exposure and disease. The data highlight that many of the imprinted genes have known associations to developmental diseases and are enriched for their role in the TP53 and AhR pathways. Assessment of the promoter regions of the imprinted genes resulted in the identification of an enrichment of binding sites for two transcription factor families, namely the zinc finger family II and PLAG transcription factors. Taken together these data contribute insight into the complex relationships between toxic metals in the environment and imprinted gene biology. View Full-Text
Keywords: imprinted genes; epigenetics; DNA methylation; TP53; aryl hydrocarbon receptor; systems biology; environmental health; toxic metals; epigenomics; environment imprinted genes; epigenetics; DNA methylation; TP53; aryl hydrocarbon receptor; systems biology; environmental health; toxic metals; epigenomics; environment
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Smeester, L.; Yosim, A.E.; Nye, M.D.; Hoyo, C.; Murphy, S.K.; Fry, R.C. Imprinted Genes and the Environment: Links to the Toxic Metals Arsenic, Cadmium and Lead. Genes 2014, 5, 477-496.

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