Overview of Epigenetic Mechanisms

Abstract

How is activity state information of a particular gene or chromosomal domain passed unchanged from parent cells to progeny cells when both the active and inactive states have the same DNA sequence? Cell memory – the faithful transmission of determined states to progeny cells – is essential for development of multicellular organisms, including plants, insects, and mammals. What epigenetic mechanisms account for cell memory? With regard to genomic imprinting, how are chromosomal domains marked as to parental source, and how is monoallelic expression in diploid cells accomplished? How can one X chromosome in mammalian cells be genetically silenced without affecting its homolog? Although these important questions have been addressed by numerous scientists for many years, we still are without complete answers. Several models to explain epigenetic phenomena have been proposed, however, and these are categorized in Table 1. These models are discussed below, and where possible, they are explained in the context of experimental examples.

Relatively simple feedback circuits can explain at least some clonally heritable epigenetic phenomena in which both alleles in diploid cells are treated similarly. This is also true for phenomena involving co-regulation of all gene copies in polytene Drosophila cells or multicopy transgenic animal or plant cells. However, meiotic heritability and phenomena showing differential treatment of identical alleles, such as X-chromosome inactivation and genomic imprinting, seem to need additional cis-limited mechanisms. It should be clearly understood that models listed in Table 1 are not mutually exclusive. On the contrary, it is very likely that more than one mechanism...