Transposable element co-option drives transcription factor neofunctionalization

ROSSPOPOFF, O.; Milovanovic, D.; Offner, S.; Lau, K.; Duhoo, Y.; Duc, J.; Planet, E.; Raclot, C.; Damery, C.; Begnis, M.; Pojer, F.; Trono, D.

doi:10.1101/2025.03.01.640934

bioRxiv · 10.1101/2025.03.01.640934

Transposable element co-option drives transcription factor neofunctionalization

ROSSPOPOFF, O.·Milovanovic, D.·Offner, S.·Lau, K.·Duhoo, Y.·Duc, J.·Planet, E.·Raclot, C.·Damery, C.·Begnis, M.·Pojer, F.·Trono, D.

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Abstract

Gene duplication and domain acquisition are key mechanisms driving protein diversification. However, the impact of these processes on the function and evolution of transcription factors (TFs) remains poorly characterized. Here, we show that the DUF3669 domain, found in a subset of KRAB zinc-finger proteins (KZFPs), originated from the co-option of a fragment of a LINE-1 transposable element ORF1p. Similar to its LINE-1-encoded ancestor, the DUF3669 domain promotes KZFPs trimerization and enables the formation of nuclear condensates with ribonucleoparticle properties, which critically influence the genomic recruitment and action of these TFs. Thus, our study uncovers a direct link between TE co-option and TF neofunctionalization, highlighting how mobile genetic elements shape the evolution of protein functionality.

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ROSSPOPOFF, O., Milovanovic, D., Offner, S., Lau, K., Duhoo, Y., Duc, J., Planet, E., Raclot, C., Damery, C., Begnis, M., Pojer, F., Trono, D.. 2025-03-06. Transposable element co-option drives transcription factor neofunctionalization. https://doi.org/10.1101/2025.03.01.640934

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