Figure 1.

Components of the epigenetic machinery. This machinery consists of writers (highlighters) and erasers of marks [for example, trimethylation of lysine 4 on histone H3 (H3K4me3)] as well as readers of those marks. A net balance between systems that remove and add a particular mark must be achieved. In many ways, the interacting epigenetic systems have certain distinct aspects that make them powerful final integrators of cellular signals (59). For instance, many of the marks placed/removed by writers/erasers can directly affect gene expression, either in a permissive (H3K4me3, shown) or nonpermissive (H3K9me3, not shown) manner. This change in expression, presumably of multiple genes, has the potential to form feedback loops by affecting the amount and availability of the modification in question. Various internal metabolites can directly affect the prevalence of marks. For instance, S-adenosyl-methionine (SAM) is a donor for methylation reactions, including both DNA and histone methylation. Use of critical metabolic intermediates like SAM as donors for histone tail modifications or for DNA methylation allows environmental influences to impact and be integrated into the system and to potentially affect gene expression directly (76).