Author:
Szyf Moshe,Meaney Michael J
Abstract
Abstract
The long-term effects of behaviour and environmental exposures, particularly during childhood, on health outcomes are well documented. Particularly thought provoking is the notion that exposures to different social environments have a long-lasting impact on human physical health. However, the mechanisms mediating the effects of the environment are still unclear. In the last decade, the main focus of attention was the genome, and interindividual genetic polymorphisms were sought after as the principal basis for susceptibility to disease. However, it is becoming clear that recent dramatic increases in the incidence of certain human pathologies, such as asthma and type 2 diabetes, cannot be explained just on the basis of a genetic drift. It is therefore extremely important to unravel the molecular links between the "environmental" exposure, which is believed to be behind this emerging incidence in certain human pathologies, and the disease's molecular mechanisms. Although it is clear that most human pathologies involve long-term changes in gene function, these might be caused by mechanisms other than changes in the deoxyribonucleic acid (DNA) sequence. The genome is programmed by the epigenome, which is composed of chromatin and a covalent modification of DNA by methylation. It is postulated here that "epigenetic" mechanisms mediate the effects of behavioural and environmental exposures early in life, as well as lifelong environmental exposures and the susceptibility to disease later in life. In contrast to genetic sequence differences, epigenetic aberrations are potentially reversible, raising the hope for interventions that will be able to reverse deleterious epigenetic programming.
Publisher
Springer Science and Business Media LLC
Subject
Pulmonary and Respiratory Medicine,Immunology,Immunology and Allergy
Reference88 articles.
1. Szyf M: Towards a pharmacology of DNA methylation. Trends Pharmacol Sci. 2001, 22: 350-4. 10.1016/S0165-6147(00)01713-2.
2. Weidle UH, Grossmann A: Inhibition of histone deacetylases: a new strategy to target epigenetic modifications for anticancer treatment. Anticancer Res. 2000, 20: 1471-85.
3. Kramer OH, Gottlicher M, Heinzel T: Histone deacetylase as a therapeutic target. Trends Endocrinol Metab. 2001, 12: 294-300. 10.1016/S1043-2760(01)00438-6.
4. Simonini MV, Camargo LM, Dong E: The benzamide MS-275 is a potent, long-lasting brain region-selective inhibitor of histone deacetylases. Proc Natl Acad Sci USA. 2006, 103: 1587-92. 10.1073/pnas.0510341103.
5. Razin A, Riggs AD: DNA methylation and gene function. Science. 1980, 210: 604-10. 10.1126/science.6254144.
Cited by
22 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献