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MET-2-Dependent H3K9 Methylation Suppresses Transgenerational Small RNA Inheritance
Itamar Lev1, Uri Seroussi1, Hila Gingold1
1Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
Current Biology : CB
|March 28, 2017
Summary
Changes in histone modifications influence transgenerational epigenetic effects in C. elegans. MET-2 protein normally inhibits small RNA inheritance, and its absence leads to permanent RNA interference responses across generations.
Area of Science:
- Epigenetics
- Molecular Biology
- Genetics
Background:
- Chromatin alterations in C. elegans can lead to transgenerational effects, including lifespan changes and fertility loss.
- Heritable small RNAs derived from double-stranded RNA can induce inheritance of histone modifications.
Purpose of the Study:
- Investigate the role of MET-2 and HRDE-1 in the mortal germline phenotype in C. elegans.
- Determine how MET-2 influences small RNA inheritance and RNA interference (RNAi) persistence across generations.
Main Methods:
- Analysis of met-2 mutants in C. elegans.
- Studying the function of HRDE-1 (an argonaute) in small RNA inheritance.
- Assessing transgenerational misexpression of small RNAs and RNAi responses.
Main Results:
- The mortal germline phenotype in met-2 mutants depends on HRDE-1 and involves accumulated transgenerational small RNA misexpression.
- MET-2 inhibits small RNA inheritance; its absence causes permanent RNAi responses lasting over 30 generations.
- Potentiation of heritable RNAi in met-2 mutants results from global hyperactivation of the small RNA inheritance machinery.
Conclusions:
- Histone modifications, regulated by MET-2, play a critical role in controlling the potency of small RNA inheritance.
- Changes in histone modifications can mediate significant transgenerational epigenetic effects by modulating small RNA inheritance pathways.
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