The marks, mechanisms and memory of epigenetic states in mammals

It is well recognized that there is a surprising degree of phenotypic varia tion among genetically identical individuals, even when the environmental i nfluences, in the strict sense of the word, are identical. Genetic textbook s acknowledge this fact and use different terms, such as 'intangible variat ion- or developmental noise', to describe it. We believe that this intangib le variation results from the stochastic establishment of epigenetic modifi cations to the DNA nucleotide sequence. These modifications, which may invo lve cytosine methylation and chromatin remodelling, result in alterations i n gene expression which, in turn, affects the phenotype of the organism. Re cent evidence, from our work and that of others in mice, suggests that thes e epigenetic modifications, which in the past were thought to be cleared an d reset on passage through the germline, may sometimes be inherited to the next generation. This is termed epigenetic inheritance, and while this proc ess has been well recognized in plants, the recent findings in mice force u s to consider the implications of this type of inheritance in mammals. At t his stage we do not know how extensive this phenomenon is in humans, but it may well turn out to be the explanation for some diseases which appear to be sporadic or show only weak genetic linkage.