Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes

Genes Dev. 2010 Oct 15;24(20):2264-9. doi: 10.1101/gad.590910.

Abstract

Noncoding RNAs are important components of regulatory networks controlling the epigenetic state of chromatin. We analyzed the role of pRNA (promoter-associated RNA), a noncoding RNA that is complementary to the rDNA promoter, in mediating de novo CpG methylation of rRNA genes (rDNA). We show that pRNA interacts with the target site of the transcription factor TTF-I, forming a DNA:RNA triplex that is specifically recognized by the DNA methyltransferase DNMT3b. The results reveal a compelling new mechanism of RNA-dependent DNA methylation, suggesting that recruitment of DNMT3b by DNA:RNA triplexes may be a common and generally used pathway in epigenetic regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Chromatin Immunoprecipitation
  • CpG Islands / genetics
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA / chemistry
  • DNA / genetics
  • DNA Methylation
  • DNA Methyltransferase 3B
  • DNA, Ribosomal / chemistry
  • DNA, Ribosomal / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Genes, rRNA / genetics*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Mice
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Mutation
  • NIH 3T3 Cells
  • Nucleic Acid Conformation
  • Promoter Regions, Genetic / genetics*
  • RNA, Untranslated / chemistry
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • Transcription Factors

Substances

  • DNA, Ribosomal
  • DNA-Binding Proteins
  • RNA, Untranslated
  • TTF1 protein, human
  • Transcription Factors
  • triplex DNA
  • Green Fluorescent Proteins
  • DNA
  • DNA (Cytosine-5-)-Methyltransferases