PT - JOURNAL ARTICLE AU - Itamar Lev AU - Hila Gingold AU - Oded Rechavi TI - H3K9me3 is Required for Inheritance of Small RNAs that Target a Unique Subset of Newly Evolved Genes AID - 10.1101/338582 DP - 2018 Jan 01 TA - bioRxiv PG - 338582 4099 - http://biorxiv.org/content/early/2018/08/19/338582.short 4100 - http://biorxiv.org/content/early/2018/08/19/338582.full AB - 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 the SET-25-dependent heritable endo-siRNAs 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.