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

Open access
Date
2019-09-16Type
- Journal Article
Citations
Cited 37 times in
Web of Science
Cited 37 times in
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ETH Bibliography
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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. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000360670Publication status
publishedExternal links
Journal / series
The EMBO JournalVolume
Pages / Article No.
Publisher
WileySubject
Coelacanth; Evolution; KAP1; KRAB zinc finger proteins; Mass spectrometryOrganisational unit
03663 - Aebersold, Rudolf (emeritus) / Aebersold, Rudolf (emeritus)
Funding
670821 - Proteomics 4D: The proteome in context (EC)
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Citations
Cited 37 times in
Web of Science
Cited 37 times in
Scopus
ETH Bibliography
yes
Altmetrics