Epigenetics

Abstract

According to its founder, Conrad Hal Waddington, epigenetics studies the causal interactions between genes and their products, which bring the phenotype into being. Waddington was the first to recognize that the developing organism is a nonlinear dynamic system and that development proceeds through a time-ordered set of epigenetic states, which are mitotically stable, but potentially reversible. The metastability of epige-netic states explains why developmental processes are buffered against minor changes in genotype and environment (a phenomenon called canalization), yet one genotype can give rise to more than one phenotype (phenotypic plasticity). Among several epigenetic inheritance systems, chromatin marking is the one that has received most attention from modern molecular biology. It has been recognized that tissue-specific gene expression patterns can be mitotically stable, because the genome is parceled into chromatin states that allow or repress use of the genetic information (permissive and repressive chromatin, respectively). Permissive and repressive chromatin states are characterized by specific patterns of DNA methylation, histone modification, and chromatin configuration. Within a cell, most often both alleles of a gene are either active or inactive. However, there are several examples where the two alleles of a gene, although identical in sequence, are functionally different. The difference can be parent-of-origin specific (as a result of genomic imprinting) or random (X inactivation and allelic exclusion). Epigenetic variation, occurring at random or induced by the environment, can lead to phenotypic variation and, in its most extreme form, to disease. In general, epigenetic states are cleared between generations. It is a matter of debate to what extent epigenetic states can be transmitted through the mammalian germline from one generation to the next.