Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region

Mol Cell Biol. 2008 Jun;28(11):3713-28. doi: 10.1128/MCB.02263-07. Epub 2008 Feb 25.


The Kcnq1ot1 antisense noncoding RNA has been implicated in long-range bidirectional silencing, but the underlying mechanisms remain enigmatic. Here we characterize a domain at the 5' end of the Kcnq1ot1 RNA that carries out transcriptional silencing of linked genes using an episomal vector system. The bidirectional silencing property of Kcnq1ot1 maps to a highly conserved repeat motif within the silencing domain, which directs transcriptional silencing by interaction with chromatin, resulting in histone H3 lysine 9 trimethylation. Intriguingly, the silencing domain is also required to target the episomal vector to the perinucleolar compartment during mid-S phase. Collectively, our data unfold a novel mechanism by which an antisense RNA mediates transcriptional gene silencing of chromosomal domains by targeting them to distinct nuclear compartments known to be rich in heterochromatic machinery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line
  • Cell Nucleolus / metabolism*
  • Chromatin / metabolism
  • Conserved Sequence
  • Gene Silencing*
  • Genes, Reporter
  • Humans
  • Membrane Proteins / genetics*
  • Plasmids / metabolism
  • Potassium Channels, Voltage-Gated / genetics
  • Promoter Regions, Genetic
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism*
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • Transcription, Genetic


  • Chromatin
  • KCNQ1OT1 long non-coding RNA, human
  • Membrane Proteins
  • Potassium Channels, Voltage-Gated
  • RNA, Antisense
  • RNA, Long Noncoding
  • RNA, Untranslated
  • XIST non-coding RNA