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research article

Evolutionarily recent transcription factors partake in human cell cycle regulation

Pulver, Cyril  
•
Forey, Romain  
•
Lederer, Alex R.  
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2025
Cell Genomics

The cell cycle is a fundamental process in eukaryotic biology and is accordingly controlled by a highly conserved core signaling cascade. However, whether recently evolved proteins also influence this process is unclear. Here, we systematically map the influence of evolutionarily recent transcription factors (TFs) on human cell cycle progression. We find that the genomic targets of select young TFs, many of which belong to the rapidly evolving Krüppel-associated box zinc-finger protein (KZFP) family, exhibit synchronized cell cycle expression. Systematic perturbation studies reveal that silencing recent TFs disrupts normal cell cycle progression, which we experimentally confirm for ZNF519, a simian-restricted KZFP. Furthermore, we show that the therian-specific KZFP ZNF274 sets the cell cycle expression and replication timing of hundreds of clustered genes, many of which are KZFPs. These findings highlight an underappreciated level of lineage specificity in cell cycle regulation.

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Type
research article
DOI
10.1016/j.xgen.2025.100923
Scopus ID

2-s2.0-105008901995

Author(s)
Pulver, Cyril  

École Polytechnique Fédérale de Lausanne

Forey, Romain  

École Polytechnique Fédérale de Lausanne

Lederer, Alex R.  

École Polytechnique Fédérale de Lausanne

Begnis, Martina  

École Polytechnique Fédérale de Lausanne

Rosspopoff, Olga  

École Polytechnique Fédérale de Lausanne

Carlevaro-Fita, Joana

École Polytechnique Fédérale de Lausanne

Martins, Filipe  

École Polytechnique Fédérale de Lausanne

Planet, Evarist  

École Polytechnique Fédérale de Lausanne

Duc, Julien

Nexco Analytics

Raclot, Charlène  

École Polytechnique Fédérale de Lausanne

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Date Issued

2025

Published in
Cell Genomics
Article Number

100923

Subjects

cell cycle

•

epigenetics

•

H3K9me3

•

heterochromatin

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KRAB zinc-finger proteins

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Perturb-seq

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regulation of transcription

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replication timing

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ZNF274

•

ZNF519

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LVG  
FunderFunding(s)Grant NumberGrant URL

Aclon Foundation

European Research Council

268721,694658

Swiss National Science Foundation

310030B_173337,310030_152879

Available on Infoscience
July 2, 2025
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/251818
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