Epigenetics and memigenetics

Abstract

The field of epigenetics is expanding rapidly, yet there is persistent uncertainty in the definition of the term. The word was coined in the mid-twentieth century as a descriptor of how intrinsic, yet largely unknown, forces act with genes to channel progenitor cells along pathways of differentiation. Near the end of the twentieth century, epigenetics was defined more specifically as the study of changes in gene activity states. In some definitions, only those activity states that are inherited across cell division were considered. Other definitions were broader, also including activity states that are transient, or occurring in non-dividing cells. The greatest point of disagreement in these current definitions, is if the term should concern only inherited activity states. To alleviate this disparity, an alternative term, 'memigenetics', could be used in place of epigenetics to describe inherited chromatin activity states. The advantage of this term is that it is self-defining, and would serve to emphasize the important concept of cell memory. It would also free the term epigenetics to be used in a broader sense in accord with the meaning of the prefix 'epi', that is, as a descriptor of what is 'over' DNA at any point in time.

Fig. 1

Examples of heritable epigenetic phenomena. a Neonatal mice carrying a mutation of the X-linked Atp7a (ATPase, Cu++ transporting, alpha polypeptide) gene have a low activity of tyrosinase, a copper-dependent enzyme that is required for melanin production. XY males are depigmented (centre) relative to pigmented, wild-type XY males or XX females (right). Random X chromosome inactivation (XCI) and clonal expansion in XX embryos carrying one wild-type and one mutant allele lead to depigmented and pigmented patches, as seen in the mottled female (left) [52]. Reprinted from [53]. b Toadflax wild-type flower, c toadflax peloric flower. The variant peloric flower phenotype, heritable through generations, cosegregates with DNA methylation and inactivation of the cycloidea gene. Here, methylation is probably conferring gene silencing, and maintaining this state through cell division. This type of gene inactivation, involving no change in DNA sequence, is termed an ‘epimutation’ [54]. Figures of toadflax flowers [44] reproduced with the permission of Macmillan Publishers, Ltd