MET-2-Dependent H3K9 Methylation Suppresses Transgenerational Small RNA Inheritance

Itamar Lev, Uri Seroussi, Hila Gingold, Roberta Bril, Sarit Anava, Oded Rechavi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

In C. elegans, alterations to chromatin produce transgenerational effects, such as inherited increase in lifespan and gradual loss of fertility. Inheritance of histone modifications can be induced by double-stranded RNA-derived heritable small RNAs. Here, we show that the mortal germline phenotype, which is typical of met-2 mutants, defective in H3K9 methylation, depends on HRDE-1, an argonaute that carries small RNAs across generations, and is accompanied by accumulated transgenerational misexpression of heritable small RNAs. We discovered that MET-2 inhibits small RNA inheritance, and, as a consequence, induction of RNAi in met-2 mutants leads to permanent RNAi responses that do not terminate even after more than 30 generations. We found that potentiation of heritable RNAi in met-2 animals results from global hyperactivation of the small RNA inheritance machinery. Thus, changes in histone modifications can give rise to drastic transgenerational epigenetic effects, by controlling the overall potency of small RNA inheritance.

Original languageEnglish
Pages (from-to)1138-1147
Number of pages10
JournalCurrent Biology
Volume27
Issue number8
DOIs
StatePublished - 24 Apr 2017

Funding

FundersFunder number
Efrat Glick Saar from the Sheba Cancer Research Institute
Geut Sulami
National Institutes of HealthSX1263, GW638, P40 OD010440
European Research Council335624

    Keywords

    • C. elegans
    • H3K9me
    • HRDE-1
    • MET-2
    • RNAi
    • epigenetic inheritance
    • histone methylation
    • mortal germline
    • small RNAs
    • transgenerational inheritance

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