H3K9me3 is required for inheritance of small RNAs that target a unique subset of newly evolved genes

• Main Authors: Itamar Lev, Hila Gingold, Oded Rechavi
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2019-03-01
• Series: eLife
• Subjects: epigenetics; small RNA; histone methylation; RNAi; H3K9; transgenerational
• Online Access: https://elifesciences.org/articles/40448

In Caenorhabditis elegans, RNA interference (RNAi) responses can transmit across generations via small RNAs. RNAi inheritance is associated with Histone-3-Lysine-9 tri-methylation (H3K9me3) of the targeted genes. In other organisms, maintenance of silencing requires a feed-forward loop between H3K9me3 and small RNAs. Here, we show that in C. elegans not only is H3K9me3 unnecessary for inheritance, the modification’s function depends on the identity of the RNAi-targeted gene. We found an asymmetry in the requirement for H3K9me3 and the main worm H3K9me3 methyltransferases, SET-25 and SET-32. Both methyltransferases promote heritable silencing of the foreign gene gfp, but are dispensable for silencing of the endogenous gene oma-1. Genome-wide examination of heritable endogenous small interfering RNAs (endo-siRNAs) revealed that endo-siRNAs that depend on SET-25 and SET-32 target newly acquired and highly H3K9me3 marked genes. Thus, ‘repressive’ chromatin marks could be important specifically for heritable silencing of genes which are flagged as ‘foreign’, such as gfp.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).