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

Natasha E. Weiser, Danny X. Yang, Suhua Feng, Natallia Kalinava, Kristen C. Brown, Jayshree Khanikar, Mallory A. Freeberg, Martha J. Snyder, Györgyi Csankovszki, Raymond C. Chan, Sam G. Gu, Taiowa A. Montgomery, Steven E. Jacobsen, John K. Kim

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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 endo-siRNAs 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.

Original languageEnglish (US)
Pages (from-to)408-423.e7
JournalDevelopmental Cell
Volume41
Issue number4
DOIs
StatePublished - May 22 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Keywords

  • epigenetic inheritance
  • germline
  • heterochromatin
  • histone modification
  • microrchidia
  • nuclear RNAi
  • small RNA

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