Epigenetics and human disease: translating basic biology into clinical applications

Abstract

Epigenetics refers to the study of heritable changes in gene expression that occur without a change in DNA sequence. Research has shown that epigenetic mechanisms provide an "extra" layer of transcriptional control that regulates how genes are expressed. These mechanisms are critical components in the normal development and growth of cells. Epigenetic abnormalities have been found to be causative factors in cancer, genetic disorders and pediatric syndromes as well as contributing factors in autoimmune diseases and aging. In this review, we examine the basic principles of epigenetic mechanisms and their contribution to human health as well as the clinical consequences of epigenetic errors. In addition, we address the use of epigenetic pathways in new approaches to diagnosis and targeted treatments across the clinical spectrum.

Fig 1: (A) Schematic of epigenetic modifications. Strands of DNA are wrapped around histone octamers, forming nucleosomes. These nucleosomes are organized into chromatin, the building block of a chromosome. Reversible and site-specific histone modifications occur at multiple sites through acetylation, methylation and phosphorylation. DNA methylation occurs at 5-position of cytosine residues in a reaction catalyzed by DNA methyltransferases (DNMTs). Together, these modifications provide a unique epigenetic signature that regulates chromatin organization and gene expression. (B) Schematic of the reversible changes in chromatin organization that influence gene expression: genes are expressed (switched on) when the chromatin is open (active), and they are inactivated (switched off) when the chromatin is condensed (silent). White circles = unmethylated cytosines; red circles = methylated cytosines.

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