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,