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Special Communication |

Epigenetics at the Epicenter of Modern Medicine

Andrew P. Feinberg, MD, MPH
JAMA. 2008;299(11):1345-1350. doi:10.1001/jama.299.11.1345.
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Epigenetics, the study of non-DNA sequence−related heredity, is at the epicenter of modern medicine because it can help to explain the relationship between an individual's genetic background, the environment, aging, and disease. It can do so because the epigenetic state varies among tissues and during a lifetime, whereas the DNA sequence remains essentially the same. As cells adapt to a changing internal and external environment, epigenetic mechanisms can remember these changes in the normal programming and reprogramming of gene activity. The common disease genetic and epigenetic (CDGE) model provides an epidemiologic framework that can incorporate epigenetic with genetic variation in the context of age-related susceptibility to disease. Under CDGE, the epigenetic program can modify the effects of deleterious genes or may be influenced by an adverse environment. Thus, including epigenetics into epidemiologic studies of human disease may help explain the relationship between the genome and the environment and may provide new clues to modifying these effects in disease prevention and therapy.

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Figure 1. Types of Epigenetic Information and Epigenetic Inheritance
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A, Types of epigenetic information. The term epigenetics refers to modifications of DNA or associated factors—aside from variations in the primary DNA sequence—that carry information content and are maintained during cell division. Examples of epigenetic modifications are DNA methylation, histone modifications, occupancy of chromatin factors, and changes in chromatin structure. CTCF indicates CCCTC-binding factor. B, Inheritance of DNA methylation. In somatic cells, epigenetic information is replicated during mitosis along with the DNA sequence. The mechanism for replication of DNA methylation is well understood but the mechanism for replication of histone modifications is not.

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Figure 2. Life Cycle of the Epigenome
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Unlike the DNA sequence, the epigenetic code changes during one's lifetime in ways specific to a given cell type. Shown here are a sperm, which is highly methylated, and an egg, which is not. After fertilization, there is a wave of demethylation that spares imprinted marks (dark brown). Tissue-specific methylation patterns emerge during later embryonic development. Age-related hypermethylation or hypomethylation could theoretically impair or enhance normal gene responsiveness to environmental signals.

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