Take a walk on the KRAB side

Canonical Krüppel-associated box (KRAB)-containing zinc finger proteins (KZFPs) act as major repressors of transposable elements (TEs) via the KRAB-mediated recruitment of the heterochromatin scaffold KRAB-associated protein (KAP)1. KZFP genes emerged some 420 million years ago in the last common ancestor of coelacanth, lungfish, and tetrapods, and dramatically expanded to give rise to lineage-specific repertoires in contemporary species paralleling their TE load and turnover. However, the KRAB domain displays sequence and function variations that reveal repeated diversions from a linear TE-KZFP trajectory. This Review summarizes current knowledge on the evolution of KZFPs and discusses how ancestral noncanonical KZFPs endowed with variant KRAB, SCAN or DUF3669 domains have been utilized to achieve KAP1-independent functions.