articleNature CommunicationsJan 9, 2026GOLD OA

A SET domain-containing protein and HCF-1 maintain transgenerational epigenetic memory

University of Cambridge · The Gurdon Institute · +5 more institutions

PubMed
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Abstract

Transgenerational epigenetic inheritance (TEI) allows epigenetic information to pass across generations through mechanisms such as small RNAs and histone modifications. Histone methylation is often deposited by SET domain-containing methyltransferases. Some SET proteins lack catalytic activity but still regulate chromatin and gene expression. Here, we characterize SET-24, a catalytically inactive SET domain protein that localizes to germline nuclei and is essential for germline immortality in Caenorhabditis elegans. In set-24 mutants, small RNA-mediated epigenetic silencing is impaired. Proteomic, yeast two-hybrid, and pull-down assays show that SET-24 interacts with HCF-1, a chromatin factor linked to…

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