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

Dev Cell. 2017 May 22;41(4):408-423.e7. doi: 10.1016/j.devcel.2017.04.023.

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.

Keywords: epigenetic inheritance; germline; heterochromatin; histone modification; microrchidia; nuclear RNAi; small RNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Nucleus / metabolism
  • Chromatin / metabolism*
  • Genome
  • Germ Cells / cytology
  • Germ Cells / metabolism*
  • Heterochromatin / metabolism
  • Histones / metabolism
  • Inheritance Patterns / genetics*
  • Lysine / metabolism
  • Methylation
  • Models, Biological
  • Mutation / genetics
  • Nuclear Proteins / metabolism*
  • RNA Interference*
  • RNA, Small Interfering / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Chromatin
  • Heterochromatin
  • Histones
  • MORC-1 protein, C elegans
  • Nuclear Proteins
  • RNA, Small Interfering
  • Lysine