Evolutionarily recent transcription factors partake in human cell cycle regulation

Area of Science:

• Eukaryotic cell biology
• Molecular biology
• Genomics

Background:

• The cell cycle, a fundamental eukaryotic process, is governed by conserved signaling pathways.
• The role of recently evolved proteins, such as transcription factors, in cell cycle regulation remains largely unexplored.

Purpose of the Study:

• To systematically investigate the impact of evolutionarily recent transcription factors (TFs) on human cell cycle progression.
• To identify specific recent TFs and their genomic targets involved in cell cycle control.

Main Methods:

• Genomic mapping of transcription factor targets.
• Analysis of cell cycle-dependent gene expression.
• Systematic perturbation studies (gene silencing).
• Experimental validation using ZNF519 and ZNF274.

Main Results:

• Genomic targets of select young TFs, including Krüppel-associated box zinc-finger proteins (KZFPs), display synchronized cell cycle expression.
• Silencing recent TFs leads to disruptions in normal cell cycle progression.
• The simian-restricted KZFP ZNF519 and therian-specific KZFP ZNF274 were experimentally confirmed to impact cell cycle regulation.
• ZNF274 regulates the cell cycle expression and replication timing of numerous clustered genes, many of which are KZFPs.

Conclusions:

• Evolutionarily recent transcription factors play a crucial, underappreciated role in regulating the cell cycle.
• The findings reveal significant lineage specificity in cell cycle control, mediated by recently evolved proteins like KZFPs.