A brief history of epigenetics

Abstract

The term "epigenetics" was originally used to denote the poorly understood processes by which a fertilized zygote developed into a mature, complex organism. With the understanding that all cells of an organism carry the same DNA, and with increased knowledge of mechanisms of gene expression, the definition was changed to focus on ways in which heritable traits can be associated not with changes in nucleotide sequence, but with chemical modifications of DNA, or of the structural and regulatory proteins bound to it. Recent discoveries about the role of these mechanisms in early development may make it desirable to return to the original definition of epigenetics.

Figure 1.

Propagation of epigenetic marks. (A) A general mechanism for propagating a histone modification such as H3K9 methylation typically found in heterochromatic regions. The modified histone tail (M) interacts with a protein binder (B) that has a binding site specific for that modification. B also has a specific interaction site with an enzyme “writer” (W) that carries out the same histone modification on an adjacent nucleosome (gray cylinder). Spreading of the histone mark will continue until the modifying machinery reaches a boundary element, delineating the boundary between heterochromatin and euchromatin. (B) A general mechanism for maintaining a histone modification during replication. Newly deposited nucleosomes (yellow), which may incorporate histone variants, are interspersed with parental nucleosomes (shaded in gray) following DNA replication. The modified histone tail (M) on the parental nucleosome interacts with a protein binder (B). As in A, B interacts with a “writer” (W), which catalyzes a histone modification on the histone tail from an adjacent daughter nucleosome.