DNA Methylation

Abstract

Multicellular organisms develop and produce hundreds of different cellular phenotypes for the most part without any purposeful change to the primary sequence of the genome. An invariant genotype can create such phenotypic diversity by employing selectivity in its pattern of gene expression. It is easy to envision that cellular phenotype results from an interplay between the information encoded in the genome and external signals that direct the subset of genes to be expressed. What is perhaps more difficult to understand is how stability in this cellular phenotype is achieved. Immortalized fibroblast cell lines can be grown in culture for decades and still be quite recognizable as fibroblasts. Obviously, these cells are not behaving like fibroblasts as a consequence of their quite artificial environment dictating that they should behave like fibroblasts. Their phenotype has apparently been internally stabilized, yet without any hardwired genetic changes. Such a mitotically (or meiotically) heritable state of gene activity that is not attributable to a change in the primary DNA sequence is referred to as an epigenetic state. The contrasting demands put on epigenetic mechanisms are, on the one hand, a high degree of flexibility during embryonic development, and on the other, an impressive amount of stability in the subsequent adult years.