PT - JOURNAL ARTICLE AU - Lianna Schwartz-Orbach AU - Chenzhen Zhang AU - Simone Sidoli AU - Richa Amin AU - Diljeet Kaur AU - Anna Zhebrun AU - Julie Ni AU - Sam Gu TI - <em>C. elegans</em> nuclear RNAi factor SET-32 deposits the transgenerational heritable histone modification, H3K23me3 AID - 10.1101/2020.02.19.956656 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.02.19.956656 4099 - http://biorxiv.org/content/early/2020/02/20/2020.02.19.956656.short 4100 - http://biorxiv.org/content/early/2020/02/20/2020.02.19.956656.full AB - Nuclear RNAi provides a highly tractable system to study RNA-mediated chromatin changes and epigenetic inheritance. Recent studies have indicated that the regulation and function of nuclear RNAi-mediated heterochromatin are highly complex. Our knowledge of histone modifications and the corresponding histone modifying enzymes involved in the system remains limited. In this study, we show that the heterochromatin mark, H3K23me3, is induced by nuclear RNAi at both exogenous and endogenous targets in C. elegans. In addition, dsRNA-induced H3K23me3 can be inherited for four generations. We demonstrate that the histone methyltransferase SET-32, methylates H3K23 in vitro. Both set-32 and the germline nuclear RNAi Argonaute, hrde-1, are required for nuclear RNAi-induced H3K23me3 in vivo. Our data poise H3K23me3 as an additional chromatin modification in the nuclear RNAi pathway and provides the field with a new target for uncovering the role of heterochromatin in transgenerational epigenetic silencing.