KRAB zinc finger protein diversification drives mammalian interindividual methylation variability
Tessa M. Bertozzi, Jessica L. Elmer, Todd S. Macfarlan, Anne C. Ferguson‐Smith
Abstract
Significance Transposable elements (TEs) are repetitive sequences with potential to mobilize, causing genetic diversity. To restrict this, most TEs in the mouse are heavily epigenetically modified by DNA methylation. However, a few TEs exhibit variable methylation levels that differ between individuals and confer an epigenetic, rather than genetic, influence on phenotype. The mechanism underlying this remains unknown. We report the identification of a polymorphic cluster of KRAB zinc finger proteins (KZFPs) responsible for the epigenetic properties of these variably methylated TEs, with deletion of the cluster profoundly influencing their DNA methylation and expression of adjacent genes. We propose that rapid KZFP divergence underlies variable epigenetic states in mammals, with implications for epigenetically conferred phenotypic differences between individuals within and across generations.