KRAB zinc-finger proteins (KZFPs) are the most abundant family of DNA-binding proteins in humans and primarily induce the epigenetic silencing of transposable elements. While KZFPs use this ability to control the transposition potential of transposable elements, they can also act as epigenetic switches that gate transposable element-derived cis -regulatory modules in a cell context-specific manner. In this way, they participate in the domestication of mobile elements, expanding their ability to establish complex gene regulatory networks. In this Perspective, we discuss emerging evidence that mutations in KZFP genes can explain human disorders and that there is a need to understand the effect of mutations in their transposable element targets. We argue that increased focus on this large yet historically understudied family will greatly contribute to addressing gaps in our understanding of cell lineage specification during development, human phenotypes and related pathologies.
Davis et al. (Fri,) studied this question.