Epigenetic inheritance of coat colour

Abstract

The ability to propagate stable states of chromatin activity is essential for normal animal development; however, little is known about the mechanisms that maintain these heritable chromatin states. Morgan et al.1 Morgan H.D. et al. Epigenetic inheritance at the agouti locus in the mouse. Nat. Genet. 1999; 23: 314-318 Crossref PubMed Scopus (1106) Google Scholar exploited the dominant mouse Avy mutation to look at epigenetic inheritance at this locus. This mutation causes variable ectopic expression of the agouti protein in hair follicles, such that Avy offspring of Avy animals exhibit a spectrum of coat-colour phenotypes, ranging from yellow (ectopic expression of the agouti gene) to full agouti (no ectopic silencing of the agouti gene). Variable expression of the Avy allele in Avy progeny is caused by the variable activity of an adjacent retroposon. However, it is also influenced by the maternal phenotype: Avy mothers with an agouti coat give birth to more offspring with an agouti phenotype, whereas Avy mothers with a yellow coat give birth to more offspring with yellow and mottled phenotypes. Morgan et al. found that the Avy allele is more extensively methylated in Avy offspring with an agouti coat than in Avy offspring with a yellow coat, indicating that chromatin modifications associated with the state of transcriptional activity at the maternal Avy allele are transmitted to the offspring. By embryo transfer experiments and genetic crosses, Morgan et al. excluded the maternal environment as a factor influencing Avy phenotypes, emphasizing the significance of the maternally transmitted chromatin modifications to gene silencing at this locus.