MET-2-Dependent H3K9 Methylation Suppresses Transgenerational Small RNA Inheritance.
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.
Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
Itamar
I
Lev
Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
Uri
U
Seroussi
Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
Hila
H
Gingold
Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
Roberta
R
Bril
Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
Sarit
S
Anava
Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: odedrechavi@gmail.com.
Oded
O
Rechavi
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D019175:DNA Methylation; D005854:Germ Cells; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D040582:Inheritance Patterns; D010641:Phenotype; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D006657:Histones; D034741:RNA, Small Interfering; D011495:Histone-Lysine N-Methyltransferase; C523531:Met-2 protein, C elegans
C. elegans; H3K9me; HRDE-1; MET-2; RNAi; epigenetic inheritance; histone methylation; mortal germline; small RNAs; transgenerational inheritance