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The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification.

Published version
Peer-reviewed

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Type

Article

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Authors

Helleboid, Pierre-Yves 
Heusel, Moritz 
Duc, Julien 
Piot, Cécile 
Thorball, Christian W 

Abstract

Krüppel-associated box (KRAB)-containing zinc finger proteins (KZFPs) are encoded in the hundreds by the genomes of higher vertebrates, and many act with the heterochromatin-inducing KAP1 as repressors of transposable elements (TEs) 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 KZFPs. Consistent with their targeting of TEs, most KZFPs conserved up to placental mammals essentially recruit KAP1 and associated effectors. In contrast, a subset of more ancient KZFPs rather interacts with factors related to functions such as genome architecture or RNA processing. Nevertheless, KZFPs from coelacanth, our most distant KZFP-encoding relative, bind the cognate KAP1. These results support a hypothetical model whereby KZFPs 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.

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Keywords

KAP1, KRAB zinc finger proteins, coelacanth, evolution, mass spectrometry, Animals, DNA Transposable Elements, Evolution, Molecular, Female, Fish Proteins, Fishes, HEK293 Cells, Humans, Placenta, Pregnancy, Protein Interaction Maps, Repressor Proteins, Tripartite Motif-Containing Protein 28, Zinc Fingers

Journal Title

EMBO J

Conference Name

Journal ISSN

0261-4189
1460-2075

Volume Title

38

Publisher

Springer Science and Business Media LLC