Take a walk on the KRAB side

• Published in: Trends in genetics 2023-11, Vol.39 (11), p.844-857
• Main Authors: Rosspopoff, Olga, Trono, Didier
• Format: Article
• Language: English
• Subjects: DNA Transposable Elements; DUF3669 domain; Heterochromatin; KRAB zinc finger proteins; PRDM9; Repressor Proteins - genetics; SCAN domain; Transcription Factors - genetics; transposable elements; Zinc Fingers - genetics
• ISSN: 0168-9525
• DOI: 10.1016/j.tig.2023.08.003

KRAB zinc finger proteins (KZFPs) are major epigenetic silencers of transposable elements acting through the recruitment of KRAB-associated protein (KAP)1, which acts as a scaffold for heterochromatin-inducing factors. Recent studies highlight the diversity of this protein family both within and between species in the vertebrate lineage.Evolutionary analyses trace back the emergence of KZFP genes to the last common ancestor of tetrapods and bony fishes, some 420 million years ago. Recent data suggests that, despite divergences in the KRAB consensus sequence, the KZFP–KAP1 relationship has been maintained throughout the vertebrate lineage.While most KZFPs are potent KAP1 recruiters and transcriptional repressors, some family members have acquired alternative KAP1-independent functions, notably through the evolution of variant KRAB sequences or the acquisition of SCAN or DUF3669 accessory domains. 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. 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 KRA