4.7 Article

MORC-1 Integrates Nuclear RNAi and Transgenerational Chromatin Architecture to Promote Germline Immortality

Journal

DEVELOPMENTAL CELL
Volume 41, Issue 4, Pages 408-+

Publisher

CELL PRESS
DOI: 10.1016/j.devcel.2017.04.023

Keywords

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Funding

  1. NIH Office of Research Infrastructure Programs [P40 OD010440]
  2. American Cancer Society [RSG RMC-125264]
  3. NIH [R01 GM118875, T32-HD007505, T32-GM007315, T32-GM007544-34, R01 GM60398, R01 GM111752, R35 GM119775, R01 GM093173, R01 GM079533]
  4. Pew Charitable Trusts
  5. Boettcher Foundation [003614-00002]
  6. Direct For Computer & Info Scie & Enginr
  7. Office of Advanced Cyberinfrastructure (OAC) [1445604] Funding Source: National Science Foundation

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Germline-expressed endogenous small interfering RNAs (endo-siRNAs) transmit multigenerational epigenetic information to ensure fertility in subsequent generations. In Caenorhabditis elegans, nuclear RNAi ensures robust inheritance of endosiRNAs and deposition of repressive H3K9me3 marks at target loci. How target silencing is maintained in subsequent generations is poorly understood. We discovered that morc-1 is essential for transgenerational fertility and acts as an effector of endo-siRNAs. Unexpectedly, morc-1 is dispensable for siRNA inheritance but is required for target silencing and maintenance of siRNA-dependent chromatin organization. A forward genetic screen identified mutations in met-1, which encodes an H3K36 methyltransferase, as potent suppressors of morc-1(-) and nuclear RNAi mutant phenotypes. Further analysis of nuclear RNAi and morc-1(-) mutants revealed a progressive, met-1-dependent enrichment of H3K36me3, suggesting that robust fertility requires repression of MET-1 activity at nuclear RNAi targets. Without MORC-1 and nuclear RNAi, MET-1-mediated encroachment of euchromatin leads to detrimental decondensation of germline chromatin and germline mortality.

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