A major epigenetic programming mechanism guided by piRNAs

Dev Cell. 2013 Mar 11;24(5):502-16. doi: 10.1016/j.devcel.2013.01.023. Epub 2013 Feb 21.

Abstract

A central enigma in epigenetics is how epigenetic factors are guided to specific genomic sites for their function. Previously, we reported that a Piwi-piRNA complex associates with the piRNA-complementary site in the Drosophila genome and regulates its epigenetic state. Here, we report that Piwi-piRNA complexes bind to numerous piRNA-complementary sequences throughout the genome, implicating piRNAs as a major mechanism that guides Piwi and Piwi-associated epigenetic factors to program the genome. To test this hypothesis, we demonstrate that inserting piRNA-complementary sequences to an ectopic site leads to Piwi, HP1a, and Su(var)3-9 recruitment to the site as well as H3K9me2/3 enrichment and reduced RNA polymerase II association, indicating that piRNA is both necessary and sufficient to recruit Piwi and epigenetic factors to specific genomic sites. Piwi deficiency drastically changed the epigenetic landscape and polymerase II profile throughout the genome, revealing the Piwi-piRNA mechanism as a major epigenetic programming mechanism in Drosophila.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Argonaute Proteins / genetics*
  • Chromatin / genetics
  • Chromatin Immunoprecipitation
  • Chromosomal Proteins, Non-Histone / genetics*
  • DNA Transposable Elements / genetics
  • Drosophila / genetics*
  • Drosophila Proteins / genetics*
  • Epigenomics*
  • Genome*
  • Genomics
  • Methyltransferases / genetics*
  • Mutation / genetics
  • RNA Polymerase II / metabolism
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Argonaute Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA Transposable Elements
  • Drosophila Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • piwi protein, Drosophila
  • heterochromatin-specific nonhistone chromosomal protein HP-1
  • Methyltransferases
  • SU(VAR)3-9
  • RNA Polymerase II