piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans

Cell. 2012 Jul 6;150(1):88-99. doi: 10.1016/j.cell.2012.06.018. Epub 2012 Jun 25.


Transgenerational effects have wide-ranging implications for human health, biological adaptation, and evolution; however, their mechanisms and biology remain poorly understood. Here, we demonstrate that a germline nuclear small RNA/chromatin pathway can maintain stable inheritance for many generations when triggered by a piRNA-dependent foreign RNA response in C. elegans. Using forward genetic screens and candidate approaches, we find that a core set of nuclear RNAi and chromatin factors is required for multigenerational inheritance of environmental RNAi and piRNA silencing. These include a germline-specific nuclear Argonaute HRDE1/WAGO-9, a HP1 ortholog HPL-2, and two putative histone methyltransferases, SET-25 and SET-32. piRNAs can trigger highly stable long-term silencing lasting at least 20 generations. Once established, this long-term memory becomes independent of the piRNA trigger but remains dependent on the nuclear RNAi/chromatin pathway. Our data present a multigenerational epigenetic inheritance mechanism induced by piRNAs.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Epigenomics*
  • Female
  • Germ Cells / metabolism
  • Male
  • RNA Interference*
  • RNA, Helminth / metabolism*
  • RNA, Small Interfering / metabolism*
  • Transgenes


  • RNA, Helminth
  • RNA, Small Interfering

Associated data

  • GEO/GSE37433
  • GEO/GSE38813