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The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification
Author(s) -
Helleboid PierreYves,
Heusel Moritz,
Duc Julien,
Piot Cécile,
Thorball Christian W,
Coluccio Andrea,
Pontis Julien,
Imbeault Michaël,
Turelli Priscilla,
Aebersold Ruedi,
Trono Didier
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018101220
Subject(s) - biology , krüppel , exaptation , zinc finger , transposable element , genome , interactome , repressor , genetics , evolutionary biology , gene , computational biology , gene expression , transcription factor
Krüppel‐associated box ( KRAB )‐containing zinc finger proteins ( KZFP s) are encoded in the hundreds by the genomes of higher vertebrates, and many act with the heterochromatin‐inducing KAP 1 as repressors of transposable elements ( TE s) during early embryogenesis. Yet, their widespread expression in adult tissues and enrichment at other genetic loci indicate additional roles. Here, we characterized the protein interactome of 101 of the ~350 human KZFP s. Consistent with their targeting of TE s, most KZFP s conserved up to placental mammals essentially recruit KAP 1 and associated effectors. In contrast, a subset of more ancient KZFP s rather interacts with factors related to functions such as genome architecture or RNA processing. Nevertheless, KZFP s from coelacanth, our most distant KZFP ‐encoding relative, bind the cognate KAP 1. These results support a hypothetical model whereby KZFP s first emerged as TE ‐controlling repressors, were continuously renewed by turnover of their hosts’ TE loads, and occasionally produced derivatives that escaped this evolutionary flushing by development and exaptation of novel functions.