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The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome
Dolinoy, D. C. (2008). The agouti mouse model: An epigenetic biosensor for nutritional and environmental alteraltion on the fetal epigenome. Nutritional Review, 66(Suppl 1), S7-11. http://doi.org/10.1111/j.1753-4887.2008.00056.x.The
McGee SL, Hargreaves M.
Histone modifications and exercise adaptations.
J Appl Physiol 110: 258–263, 2011. First published October 28, 2010; doi:10.1152/japplphysiol.00979.2010.
—The spatial association between genomic DNA and histone proteins within chromatin plays a key role in the regulation of gene expression and is largely governed by post-translational modifications to histone proteins, particularly H3 and H4. These modifications include phosphory- lation, acetylation, and mono-, di-, and tri-methylation, and while some are associated with transcriptional repression, acetylation of lysine residues within H3 generally correlates with transcriptional activation. Histone acetylation is regulated by the balance between the activities of histone acetyl transferase (HAT) and histone deacetylase (HDAC). In skeletal muscle, the class II HDACs 4, 5, 7, and 9 play a key role in muscle development and adaptation and have been implicated in exercise adaptations. As just one example, exercise results in the nuclear export of HDACs 4 and 5, secondary to their phosphorylation by CaMKII and AMPK, two kinases that are activated during exercise in response to changes in sarcoplasmic Ca2⫹levels and energy status, in association with increased GLUT4 expression in human skeletal muscle. Unraveling the complexities of the so-called “histone code” before and after exercise is likely to lead to a greater understanding of the regulation of exercise/activity-induced alterations in skeletal muscle gene expression and reinforce the importance of skeletal muscle plasticity in health and disease.
Mcgee, S. L., & Hargreaves, M. (2012). Histone modifications and exercise adaptations signals mediating skeletal muscle remodeling by activity histone modifications and exercise adaptations. Journal of Applied Physiology, 110, 258–263. http://doi.org/10.1152/japplphysiol.00979.2010
Epigenetic mechanisms for nutrition determinants of later health outcomes
Epigenetic marking on genes can determine whether or not genes are expressed. Epigenetic regulation is mediated by the addition of methyl groups to DNA cytosine bases, of methyl and acetyl groups to proteins (histones) around which DNA is wrapped, and by small interfering RNA molecules. Some components of epigenetic regula- tion have evolved to permit control of whether maternal or paternal genes are expressed. The epigenetic imprinting of IGF2 expression is an example of maternal and paternal epigenetic marking that mod- ulates fetal growth and fetal size. However, epigenetic regulation also permits the fetus and the infant to adapt gene expression to the environment in which it is growing; sometimes when this adjust- ment goes awry, the risk of chronic disease is increased. Recent progress in the understanding of nutritional influences on epige- netics suggests that nutrients that are part of methyl-group metab- olism can significantly influence epigenetics. During critical periods in development, dietary methyl-group intake (choline, methionine, and folate) can alter DNA and histone methylation, which results in lifelong changes in gene expression. In rodent models, pregnant dams that were fed diets high in methionine, folic acid, and choline produced offspring with different coat colors or with kinked tails. A number of syndromes in humans can be caused by defective epigenetic regulation, including Rett syndrome. There are interest- ing examples of the effects of nutrition in early life that result in altered health in adults, and some of these could be the result of altered epigenetic regulation of gene expression. Am J Clin Nutr 2009;89(suppl):1488S–93S.
Zeisel, S. H. (2009). Epigenetic mechanisms for nutrition determinants of later health outcomes. American Journal of Clinical Nutrition, 89(suppl), 1488S–1493S. http://doi.org/10.3945/ajcn.2009.27113B.1
NIH Public Access
Author Manuscript Birth Defects Res A Clin Mol Teratol. Author manuscript; available in PMC 2011 October 1. Published in final edited form as: Birth Defects Res A Clin Mol Teratol. 2010 October ; 88(10): 938–944. doi:10.1002/bdra.20685.
Epigenomic Disruption: The Effects of Early Developmental Exposures Autumn J. Bernal* and Randy L. Jirtle, PhD
Department of Radiation Oncology Duke University Medical Center Durham, North Carolina, 27710 USA
Through DNA methylation, histone modifications, and small regulatory RNAs the epigenome systematically controls gene expression during development-- both in utero and throughout life. The epigenome is also a very reactionary system; its labile nature allows it to sense and respond to environmental perturbations to ensure survival during fetal growth. This pliability can lead to aberrant epigenetic modifications that persist into later life and induce numerous disease states. Endocrine disrupting compounds (EDCs) are ubiquitous chemicals that interfere with growth and development. Several EDCs also interfere with epigenetic programming. The investigation of the epigenotoxic effects of bisphenol A (BPA), an EDC used in the production of plastics and resins, has further raised concern for the impact of EDCs on the epigenome. Using the Agouti viable yellow (Avy) mouse model, dietary BPA exposure was shown to hypomethylate both the Avy and the CabpIAP metastable epialleles. This hypomethylating effect was counteracted with dietary supplementation of methyl donors or genistein. These results are consistent with reports of BPA and other EDCs causing epigenetic effects. Epigenotoxicity could lead to numerous developmental, metabolic, and behavioral disorders in exposed populations. The heritable nature of epigenetic changes also increases the risk for transgenerational inheritance of phenotypes. Thus, epigenotoxicity must be considered when assessing these compounds for safety.
Bernal, A. J., & Jirtle, R. L. (2011). Epigenomic disruption: The effects of early developmental exposures. Birth Defects, 88(10), 938–944. http://doi.org/10.1002/bdra.20685.Epigenomic