Question

What are the mechanisms by which epigenetic changes affect gene expression?

Answer 1

The term, “epigenetics,” was first used to refer to the complex interactions between the genome and the environment that are involved in development and differentiation in higher organisms. Today, this term is used to refer to heritable alterations that are not due to changes in DNA sequence. Rather, epigenetic modifications, or “tags,” such as DNA methylation and histone modification, alter DNA accessibility and chromatin structure, thereby regulating patterns of gene expression. These processes are crucial to normal development and differentiation of distinct cell lineages in the adult organism. They can be modified by exogenous influences, and, as such, can contribute to or be the result of environmental alterations of phenotype or pathophenotype. Importantly, epigenetic programming has a crucial role in the regulation of pluripotency genes, which become inactivated during differentiation. Here, we review the major mechanisms in epigenetic regulation; highlight the role of stable, long-term epigenetic modifications that involve DNA methylation; and discuss those modifications that are more flexible (short-term) and involve histone modifications, such as methylation and acetylation. We will also discuss the role of nutritional and environmental challenges in generational inheritance and epigenetic modifications, concentrating on examples that relate to complex cardiovascular diseases, and specifically dissect the mechanisms by which homocysteine modifies epigenetic tags. Lastly, we will discuss the possibilities of modifying therapeutically acquired epigenetic tags, summarizing currently available agents and speculating on future directions.



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