Murine metastable epialleles and transgenerational epigenetic inheritance

Abstract

For decades it has been recognized that a number of genes in the mouse genome do not behave according to Mendelian rules. Some of these genes exhibit unique patterns of expression, including variegation, variable expressivity in the context of isogenicity and transgenerational epigenetic inheritance. They are known as metastable epialleles. A correlation between expression and epigenetic state has been observed at these alleles, and information is emerging about the temporal course of erasure and re-establishment of these epigenetic marks during mouse development. Perhaps the most intriguing aspect of this process is the stochastic nature of the re-establishment of epigenetic state. This review aims to discuss the genomic structure and function of known and suspected metastable epialleles, to gain insight into the possible molecular mechanisms involved, and to aid in the future identification of other such alleles in the mouse and man.